Introduction: The New Medical Landscape
Koch’s postulates See early English translation: Koch R. Investigations into the Etiology of Traumatic Infective Diseases. London, England: The New Sydenham Society; 1880. http://pds.lib.harvard.edu/pds/view/7027406. Accessed June 24, 2015; Blevins SM, Bronze MS. Robert Koch and the “golden age” of bacteriology. Int J Infect Dis. 2010;14(9):e744–751. doi:10.1016/j.ijid.2009.12.003.
during World War II Oatman E. The drug that changed the world. Journal of the College of Physicians & Surgeons of Columbia University. Winter 2005;25(1). http://www.cumc.columbia.edu/psjournal/archive/winter-2005/drug.html. Accessed September 2, 2015.
the White Death, and leprosy Dormandy T. The White Death—A History of Tuberculosis. London, England: Hambledon Press; 1999.
during the nineteenth and twentieth centuries Koehler CW. Consumption, the great killer. thetimeline. mdd. 2002;5(2):47–49. http://pubs.acs.org/subscribe/archive/mdd/v05/i02/html/02timeline.html. Accessed August 30, 2015.
waiting to die Sucre R. The great white plague: the culture of death and the tuberculosis sanatorium. http://www.faculty.virginia.edu/blueridgesanatorium/death.htm. Accessed August 30, 2015.
“Sanatorium, Texas” Henderson JC. Sanatorium, TX. Handbook of Texas Online. 2010. https://tshaonline.org/handbook/online/articles/hls16. Accessed August 30, 2015.
the 1860s and 1960s Wong A. When the last patient dies. The Atlantic. May 27, 2015. http://www.theatlantic.com/health/archive/2015/05/when-the-last-patient-dies/394163/. Accessed August 30, 2015.
families to stay together Waters MF, Rees RJ, Pearson JM, et al. Rifampicin for lepromatous leprosy: nine years’ experience. Br Med J. 1978;1(6106):133–136; Zaffiri L, Gardner J, Toledo-Pereyra LH. History of antibiotics: from salvarsan to cephalosporins. J Invest Surg. 2012;25(2):67–77.
decades of the twentieth century WGBH Educational Foundation and Vulcan Productions, Inc. Deadly diseases: polio. Rx for Survival. http://www.pbs.org/wgbh/rxforsurvival/series/diseases/polio.html. Accessed August 31, 2015.
in the early 1950s Meier P. The biggest public health experiment ever: the 1954 field trial of the Salk poliomyelitis vaccine. In: Tanur JM, Mosteller F, Kruskal WH, et al. Statistics: A Guide to the Unknown. Belmont, CA: Duxbury; 1989. http://www.medicine.mcgill.ca/epidemiology/hanley/c622/salk_trial.pdf. Accessed August 31, 2015.
Basil O’Connor to run it Franklin D. Roosevelt. Whatever happened to polio? Smithsonian National Museum of American History. http://amhistory.si.edu/polio/howpolio/fdr.htm. Accessed August 31, 2015.
March of Dimes March of Dimes. Whatever happened to polio? Smithsonian National Museum of American History. http://amhistory.si.edu/howpolio/fdr.htm. Accessed August 31, 2015.
rarely reared its head since Meier P. The biggest public health experiment ever: the 1954 field trial of the Salk poliomyelitis vaccine. In: Tanur JM, Mosteller F, Kruskal WH, et al. Statistics: A Guide to the Unknown. Belmont, CA: Duxbury; 1989. http://www.medicine.mcgill.ca/epidemiology/hanley/c622/salk_trial.pdf. Accessed August 31, 2015.
those cells are microbial Stein R. Finally, a map of all the microbes on your body. NPR. June 13, 2012. http://www.npr.org/sections/health-shots/2012/06/13/154913334/finally-a-map-of-all-the-microbes-on-your-body. Accessed August 31, 2015; Sender R, Fuchs S, Milo R. Revised estimates for the numbers of human and bacteria cells in the body. bioRxiv. 2016. Preprint. January 6, 2016. doi:10.1101/036103. http://www.biorxiv/early/2016/01/06/036103.full.pdf. Accessed January 14, 2016.
no single person carries them all Mundasad S. Human microbiome project reveals largest microbial map. BBC News. June 13, 2012. http://www.bbc.com/news/health-18422288. Accessed August 30, 2015.
850 on the skin Bouslimani A, Porto C, Rath CM, et al. Molecular cartography of the human skin surface in 3D. Proc Natl Acad Sci USA. 2015;112(17), e2120–e2129; Hilty M, Burke C, Pedro H, et al. Disordered microbial communities in asthmatic airways. PLoS ONE. 2010;5(1):e8578. doi:10.1371/journal.pone.0008578.
in the urogenital tract Hummelen R, Fernandes AD, Macklaim JM, et al. Deep sequencing of the vaginal microbiota of women with HIV. PLoS ONE. 2010;5(8):e12078. doi:10.1371/journal.pone.0012078; The Scientist Staff. The body’s ecosystem. The Scientist. August 1, 2014. http://www.the-scientist.com/?articles.view/articleNo/40600/title/The-Body-s-Ecosystem/. Accessed August 31, 2015.
3,000 square inches Weyrich LS, Dixit S, Farrer AG, et al. The skin microbiome: associations between altered microbial communities and disease. Australas J Dermatol. February 25, 2015. doi:10.1111/ajd.12253; Skin. National Geographic. http://science.nationalgeographic.com/science/health-and-human-body/human-body/skin-article/. Accessed August 31, 2015.
your sweaty toes Norton A. Scientists map the fungi on your feet. U.S. News Health. May 22, 2013. http://health.usnews.com/health-news/news/articles/2013/05/22/scientists-map-the-fungi-on-your-feet. Accessed August 31, 2015.
Carl Linnaeus Paterlini M. There shall be order: the legacy of Linnaeus in the age of molecular biology. EMBO Rep. 2007;8(9):814–816.
Stephen Jay Gould Gould SJ, Ontogeny and Phylogeny. Cambridge, MA: Harvard University Press; 1977.
23 percent of deaths The top 10 causes of death. World Health Organization Fact Sheet. http://who.int/mediacentre/factsheets/fs310/en/index2.html. Accessed August 31, 2015.
87 percent of all deaths The top 10 causes of death. World Health Organization Fact Sheet. http://who.int/mediacentre/factsheets/fs310/en/index2.html. Accessed August 31, 2015.
68 percent of all deaths The top 10 causes of death. World Health Organization Fact Sheet. http://who.int/mediacentre/factsheets/fs310/en/index2.html. Accessed August 31, 2015; Bloom DE, Caliero ET, Jane-Llopis E, et al. The global economic burden of noncommunicable diseases. Geneva: World Economic Forum; 2011. http://www.weforum.org/EconomicsOfNCD.
World Health Organization Global Status Report on NCDs. Chronic diseases and health promotion. World Health Organization. http://www.who.int/chp/ncd_global_status_report/en/. Accessed June 23, 2015.
United Nations Global Status Report on NCDs. Chronic diseases and health promotion. World Health Organization. http://www.who.int/nmh/events/un_ncd_summit2011/political_declaration_en.pdf. Accessed June 23, 2015.
“incredibly selfish” Allen V. Girl, 4, went into anaphylactic shock and lost consciousness on a plane after selfish passenger ignored three warnings not to eat nuts on board. Mail Online. August 14, 2014. http://www.dailymail.co.uk/news/article-2724684/Nut-allergy-girl-went-anaphylactic-shock-plane-passenger-ignored-three-warnings-not-eat-nuts-board.html. Accessed June 18, 2015.
their country of origin Davidson NK, Moreland P. Living with diabetes blog: traveling with diabetes—plan ahead. Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/diabetes/expert-blog/traveling-with-diabetes/bgp-20056556. Accessed June 23, 2015.
stabilize blood sugar levels Davidson NK, Moreland P. Living with diabetes blog: traveling with diabetes—plan ahead. Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/diabetes/expert-blog/traveling-with-diabetes/bgp-20056556. Accessed June 18, 2015.
it was 1 in 45 Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/data/nhsr/nhsr087.pdf. Accessed November 18, 2015.
to rise to 42 percent by 2030 Finkelstein EA, Khavjou OA, Thompson H, et al. Obesity and severe obesity forecasts through 2030. Am J Prev Med. 2012;42(6):563–570.
useless to him Cooperstein P. Obese man says airline made him book 2 tickets, then gave him seats 2 rows apart. Business Insider. October 14, 2013. http://www.businessinsider.com/obese-man-says-airline-made-him-book-2-tickets-then-gave-him-seats-2-rows-apart-2013-10. Accessed June 23, 2015.
“on any of [their] aircraft” Grenoble R. Airline flies obese man to destination—then refuses to fly him home. Huff Post Travel. November 9, 2013. http://www.huffingtonpost.com/2013/11/09/too-fat-to-fly-british-airways-kevin-chenais_n_4242407.html. Accessed June 23, 2015.
lack of exercise Engber D. Fat-E: the new Pixar movie goes out of its way to equate obesity with environmental collapse. Slate. July 10, 2008. http://www.slate.com/articles/health_and_science/green_room/2008/07/fate.html. Accessed June 23, 2015.
as child abusers Luscombe R. Puerto Rico law would brand parents of obese children “child abusers.” The Guardian. March 8, 2015. http://www.theguardian.com/world/2015/mar/08/puerto-rico-childhood-obesity-law-parents-abuse. Accessed June 23, 2015.
safely entertain guests Cable A. Whiff of perfume could kill me. Mail Online. http://www.dailymail.co.uk/health/article-299652/Whiff-perfume-kill-me.html. Accessed June 28, 2015.
encouraging others to follow Indoor environmental quality policy. Office of Health and Safety. Centers for Disease Control and Prevention. http://www.drsteinemann.com/Resources/CDC%20Indoor%20Environmental%20Quality%20Policy.pdf. Accessed June 23, 2015.
fragrance-free workplace policy Scent-free policy for the workplace, OSH Answers Fact Sheets. Canadian Centre for Occupational Health and Safety. http://www.ccohs.ca/oshanswers/hsprograms/scent_free.html. Updated June 24, 2015. Accessed June 23, 2015.
many popular perfumes Wendlandt A. What’s in a scent? Perfume makers adapt to EU rules. Reuters. July 7, 2104. http://www.reuters.com/article/2014/07/07/us-perfume-regulation-insight-idUSKBN0FC0EB20140707. Accessed June 23, 2015.
Marilyn Monroe Tadeo M. Iconic Chanel No 5 perfume to reformulate under new EU regulations. Independent. May 29, 2014. http://www.independent.co.uk/news/business/news/iconic-chanel-no-5-perfume-to-reformulate-under-new-eu-regulations-9451331.html. Accessed June 18, 2015.
didn’t change; we did Tadeo M. Iconic Chanel No 5 perfume to reformulate under new EU regulations. Independent. May 29, 2014. http://www.independent.co.uk/news/business/news/iconic-chanel-no-5-perfume-to-reformulate-under-new-eu-regulations-9451331.html. Accessed June 18, 2015.
1. The End of the Old Biology
genetics and human nature Dobzhansky TG. The Biological Basis of Human Freedom. New York, NY: Columbia University Press; 1956.
“gene machines” Dawkins R. The Selfish Gene. Oxford, England: Oxford University Press; 1976.
North America, Europe, and Asia The human genome project completion: frequently asked questions. National Human Genome Research Institute. NIH. https://www.genome.gov/11006943. Accessed June 23, 2015.
journal Nature Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921.
approximately 22,000 genes Cutter AD, Dey A, Murray RL. Evolution of the Caenorhabditis elegans genome. Mol Biol Evol. 2009;26(6):1199–1234.
2012 paper I wrote Dietert RR, Dietert J. The completed self: an immunological view of the human-microbiome superorganism and risk of chronic diseases. Entropy. 2012;14(11):2036–2065. doi:10.3390/e14112036.
“fills me with astonishment” Dawkins R. The Selfish Gene. Oxford, England: Oxford University Press; 1976.
2. Superorganism Ecology
“public health and basic science” Relman DA. Microbiology: learning about who we are. Nature. 2012;486(7402):194–195.
cause malaria Malaria: malaria parasites. Centers for Disease Control and Prevention. http://www.cdc.gov/malaria/about/biology/parasites.html. Accessed June 6, 2015.
equally represented Ter Steege H, Pitman NCA, Sabatier D, et al. Hyperdominance in the Amazonian tree flora. Science. 2013;342(6156). doi:10.1126/science.1243092.
species of butterflies Rainforests: exotic, diverse and highly threatened. The Nature Conservancy. http://www.nature.org/ourinitiatives/habitats/rainforests/index.htm. Accessed June 7, 2015.
multiple scientific societies Ochwang’i DO, Kimwele CN, Oduma JA, et al. Medicinal plants used in treatment and management of cancer in Kakamega County, Kenya. J Ethnopharmacol. 2014;151(3):1040–1055.
natural antimicrobials Qin S, Li J, Chen H-H, et al. Isolation, diversity, and antimicrobial activity of rare actinobacteria from medicinal plants of tropical rain forests in Xishuangbanna, China. Appl Environ Microbiol. 2009;75(19):6176–6186.
rosy periwinkle Chivian E, Bernstein A, eds. Sustaining Life: How Human Health Depends on Biodiversity. Oxford, England: Oxford University Press; 2008.
tropical rain forests Lang SS. Tom Eisner, “father of chemical ecology” and renowned Cornell biologist, dies at 81. Cornell Chronicle. March 27, 2011. http://www.news.cornell.edu/stories/2011/03/tom-eisner-father-chemical-ecology-dies-81. Accessed June 7, 2015.
Eisner’s sensibility Ghazoul J, Sheil D. Tropical Rain Forest Ecology, Diversity, and Conservation. Oxford, England: Oxford University Press; 2010.
diversity as well Newton AC, ed. Biodiversity Loss and Conservation in Fragmented Forest Landscapes. Wallingford, England: CABI; 2007.
research team Mueller RC, Paula FS, Mirza BS, et al. Links between plant and fungal communities across a deforestation chronosequence in the Amazon rainforest. ISME J. 2014;8(7):1548–1550.
photosynthesis by the algae Barott KL, Venn AA, Perez SO, et al. Coral host cells acidify symbiotic algal microenvironment to promote photosynthesis. Proc Natl Acad Sci USA. 112(2):607–612.
urchins, and clams What species live in and around coral reefs? National Ocean Service. http://oceanservice.noaa.gov/facts/coral_species.html. Accessed June 7, 2015.
biologist David Mindell Mindell DP. Phylogenetic consequences of symbioses: Eukarya and Eubacteria are not monophyletic taxa. Biosystems. 1992;27(1):53–62. doi:10.1016/0303-2647(92)90046-2.
degradation of the coral reef Pollock FJ, Lamb JB, Field SN, et al. Sediment and turbidity associated with offshore dredging increase coral disease prevalence on nearby reefs. PLoS ONE. 2014;9(7):e102498. doi:10.1371/journal.pone.0102498.
weedy, large algae Littler MM, Littler DS, Brooks BL. Harmful algae on tropical coral reefs: bottom-up eutrophication and top-down herbivory. Harmful Algae. 2006;5(5):565–585.
bacteria, fungi, and viruses Blaser MJ. The microbiome revolution. J Clin Invest. 2014;124(10):4162–4165.
1,000 different species of bacteria Grice EA, Kong HH, Conlan S, et al. Topographical and temporal diversity of the human skin microbiome. Science. 2009;324(5931):1190–1192.
harbor approximately 1,000 different bacterial species Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65.
minority of those genes Li J, Jia H, Cai X, et al. An integrated catalog of reference genes in the human gut microbiome. Nat Biotechnol. 2014;32(8):834–841.
quarter of their genes Greenblum S, Carr R, Borenstein E. Extensive strain-level copy-number variation across human gut microbiome species. Cell. 2015;160(4):583–594.
consortium of researchers Bouslimani A, Porto C, Rath CM, et al. Molecular cartography of the human skin surface in 3D. Proc Natl Acad Sci USA. 2015;112(17):e2120–e2129.
small intestine or skin The Scientist Staff. The body’s ecosystem. The Scientist. August 1, 2014. http://www.the-scientist.com/?articles.view/articleNo/40600/title/The-Body-s-Ecosystem/. Accessed July 13, 2015.
“biome depletion” Beales DL. Biome depletion in conjunction with evolutionary mismatches could play a role in the etiology of neurofibromatosis 1. Med Hypotheses. 2015;84(4):305–314.
importance to the ecosystem Mouillot D, Bellwood DR, Baraloto C, et al. Rare species support vulnerable functions in high-diversity ecosystems. PLoS Biol. 2013;11(5):e1001569. doi:10.1371/journal.pbio.1001569.
epithelial and immune cells Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA. 2013;110(22):9066–9071; Owens B. Gut microbe may fight obesity and diabetes. Nature News. 2013. doi:10.1038/nature.2013.12975.
human mammalian species Gordon HA, Pesti L. The gnotobiotic animal as a tool in the study of host microbial relationships. Bacteriol Rev. 1971;35(4):390–429.
germ-free mice Williams SCP. Gnotobiotics. PNAS USA. 2014;111(5):1661.
in order to survive Gordon HA, Pesti L. The gnotobiotic animal as a tool in the study of host microbial relationships. Bacteriol Rev. 1971;35(4):390–429.
three days and die Hirayama K, Uetsuka K, Kuwabara Y, Tamura M, Itoh K. Vitamin K deficiency of germfree mice caused by feeding standard purified diet sterilized by gamma-irradiation. Exp Anim. 2007;56(4):273–278.
immune responses Gordon HA, Pesti L. The gnotobiotic animal as a tool in the study of host microbial relationships. Bacteriol Rev. 1971;35(4):390–429; Heneghan J, ed. Germfree Research: Biological Effect of Gnotobiotic Environments. New York, NY: Academic Press; 1973; Umesaki Y. Use of gnotobiotic mice to identify and characterize key microbes responsible for the development of the intestinal immune system. Proc Jpn Acad Ser B Phys Biol Sci. 2014;90(9):313–332.
made by the microbiome A brief history of the use of microfloras in gnotobiotic rodents. Taconic. http://www.taconic.com/prepare-your-model/preconditioning-solutions/microbiome-solutions/brief-history-of-the-use-of-microfloras-in-gnotobiotic-rodents.html. Accessed June 6, 2015.
gut bacteria are killed off Shirakawa H, Komai M, Kimura S. Antibiotic-induced vitamin K deficiency and the role of the presence of intestinal flora. Int J Vitam Nutr Res. 1990;60(3):245–251.
3. The Invisible Human Superorganism
ten million microbial genes Li J, Jia H, Cai X, et al. An integrated catalog of reference genes in the human gut microbiome. Nat Biotechnol. 2014;32(8):834–841; INRA News Office. Cataloguing 10 million human gut microbial genes: an unparalleled accomplishment. INRA Science & Impact. 2014. http://www.inra.fr/en/Scientists-Students/Mechanisms-of-living-organisms/All-the-news/Cataloguing-10-million-human-gut-microbial-genes. Accessed July 14, 2015.
very long time Weiner MS. The Rule of the Clan: What an Ancient Form of Social Organization Reveals About the Future of Individual Freedom. New York, NY: Farrar, Straus and Giroux; 2013.
continues even today Schatz E. Modern Clan Politics: The Power of “Blood” in Kazakhstan and Beyond. Seattle, WA: University of Washington Press; 2004.
Missing Microbes Blaser MJ. Missing Microbes: How the Overuse of Antibiotics Is Fueling our Modern Plagues. New York, NY: Henry Holt & Co; 2014.
what was required Dietert RR, Dietert J. Impact of women on the history of Scottish goldsmithing. History Scotland Magazine. 2011;11(6):48–53.
wealth and property Narayan A. Matrilineal society. Encyclopaedia Britannica. http://www.britannica.com/topic/matrilineal-society. Accessed July 3, 2015.
80 percent are patriarchal Divale WT, Harris M. Population, warfare, and the male supremacist complex. Am Anthropol. 1976;78(3):521–538.
patrilineal lineage Holden CJ, Sear R, Mace R. Matriliny as daughter-biased investment. Evol Hum Behav. 2003;24(2):99–112.
chapel and a padded cell Claire. The birth of Elizabeth I. The Anne Boleyn Files. 2010. http://www.theanneboleynfiles.com/the-birth-of-elizabeth-i/. Accessed July 2, 2015.
fifty-five million by the year 2020 Tsai T. China has too many bachelors. PRB. 2012. http://www.prb.org/Publications/Articles/2012/china-census-excess-males.aspx. Accessed July 2, 2015; Poston DL, Conde E, DeSalvo B. China’s unbalanced sex ratio at birth, millions of excess bachelors and societal implications. Vulnerable Child Youth Stud. 2011;6(4):314–320.
increased violence against women Trivedi A, Timmons H. India’s man problem. India Ink. The New York Times. January 16, 2013. http://india.blogs.nytimes.com/2013/01/16/indias-man-problem/. Accessed July 2, 2015.
enforcement has been problematic Hesketh T, Lu L, Xing ZW. The consequences of son preference and sex-selective abortion in China and other Asian countries. CMAJ. 2011;183(12):1374–1377.
that of the mouth Aagaard K, Ma J, Antony KM, et al. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6(237):237ra65.
Lactobacillus bacteria Zheng J, Xiao X, Zhang Q, et al. The placental microbiome varies in association with low birth weight in full-term neonates. Nutrients. 2015;7(8):6924–6937. doi:10.3390/nu7085315.
Bacteroides, and Clostridium Adlerberth I, Wold AE. Establishment of the gut microbiota in Western infants. Acta Paediatr. 2009;98(2):229–238.
carried against the mother’s skin Dietert RR. Natural childbirth and breastfeeding as preventive measures of immune-microbiome dysbiosis and misregulated inflammation. J Anc Dis Prev Rem. 2013;1:103. doi:10.4172/jadpr.1000103.
with few exceptions Dietert RR. Natural childbirth and breastfeeding as preventive measures of immune-microbiome dysbiosis and misregulated inflammation. J Anc Dis Prev Rem. 2013;1:103. doi:10.4172/jadpr.1000103.
could harm the baby Grandjean P, Satoh H, Murata K, Eto K. Adverse effects of methylmercury: environmental health research implicatons. Environ Health Perspect. 2010;118(8):1137–1145.
needed by our microbes Marcobal A, Barboza M, Froehlich JW, et al. Consumption of human milk oligosaccharides by gut-related microbes. J Agric Food Chem. 2010;58(9):5334–5340.
stages of an infant’s life Chichlowski M, German JB, Lebrilla CB, Mills DA. The influence of milk oligosaccharides on microbiota of infants: opportunities for formulas. Annu Rev Food Sci Technol. 2011;2:331–351.
baby will consume McGuire MK, McGuire MA. Human milk: Mother Nature’s prototypical probiotic food? Adv Nutr. 2015;6(1):112–123.
bacteria in breast milk Soto A, Martin V, Jiménez E, et al. Lactobacilli and bifidobacteria in human breast milk: influence of antibiotherapy and other host and clinical factors. J Pediatr Gastroenterol Nutr. 2014;59(1):78–88.
elective C-section Cabrera-Rubio R, Mira-Pascual L, Mira A, Collado MC. Impact of mode of delivery on the milk microbiota composition of healthy women. J Dev Orig Health Dis. 2016;7(1):54–60. doi:10.1017/S2040174415001397.
residence in the baby’s gut Rautava S. Early microbial contact, the breast milk microbiome and child health. J Dev Orig Health Dis. 2016;7(1)5–14; McGuire MK, McGuire MA. Human milk: Mother Nature’s prototypical probiotic food? Adv Nutr. 2015;6(1):112–123.
prior publications Dietert RR. Developmental immunotoxicology (DIT): windows of vulnerability, immune dysfunction and safety assessment. J Immunotoxicol. 2008;5(4):401–412.
affected by the microbiome Dietert RR, Etzel RA, Chen D, et al. Workshop to identify critical windows of exposure for children’s health: immune and respiratory systems work group summary. Environ Health Perspect. 2000;108(Suppl 3):483–490; Olszak T, An D, Zeissig S, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science. 2012;336(6080):489–493; Principles of pediatric environmental health: why are children often especially susceptible to the adverse effects of environmental toxicants? Environ Health Med Edu. ATSDR. 2012. http://www.atsdr.cdc.gov/csem/csem.asp?csem=27&po=3. Accessed September 4, 2015.
helping the other out Lodwig EM, Hosie AHF, Bourdès A, et al. Amino-acid cycling drives nitrogen fixation in the legume-Rhizobium symbiosis. Nature. 2003;422(6933):722–726.
upper atmosphere DeLeon-Rodriguez N, Lathem TL, Rodriguez-RLM, et al. Microbiome of the upper troposphere: species composition and prevalence, effects of tropical storms, and atmospheric implications. Proc Natl Acad Sci USA. 2013;110(7):2575–2580.
Latin into “clean” Vaishampayan P, Moissl-Eichinger C, Pukall R, et al. Description of Tersicoccus phoenicis gen. nov., sp. nov. isolated from spacecraft assembly clean room environments. Int J Syst Evol Microbiol. 2013;63(Pt 7):2463–2471.
ultraviolet radiation Vaishampayan PA, Rabbow E, Horneck G, Venkateswaran KJ. Survival of Bacillus pumilus spores for a prolonged period of time in real space conditions. Astrobiology. 2012;12(5):487–497.
humanoid communities Tito RY, Knights D, Metcalf J, et al. Insights from characterizing extinct human gut microbiomes. PLoS ONE. 2012;7(12):e51146. doi: 10.1371/journal.pone.0051146.
bacteria found in the mouth Adler CJ, Dobney K, Weyrich LS, et al. Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the Neolithic and Industrial revolutions. Nat Gen. 2013;45(4):450–455.
nucleus have mitochondria Sagan L. On the origin of mitosing cells. J Theor Biol. 1967;14(3):255–274.
Acquiring Genomes Margulis L, Sagan D. Acquiring Genomes: A Theory of the Origins of Species. New York, NY: Basic Books; 2002.
archaea and bacteria Tekle YI, Parfrey LW, Katz LA. Molecular data are transforming hypotheses on the origin and diversification of Eukaryotes. Bioscience. 2009;59(6):471–481.
our bacterial ancestors Crisp A, Boschetti C, Perry M. Expression of multiple horizontally acquired genes is a hallmark of both vertebrate and invertebrate genomes. Genome Biol. 2015;16(1):50. doi:10.1186/s.13059015-0607-3.
William Cullen Cullen WR. Is Arsenic an Aphrodisiac?: The Sociochemistry of an Element. London, England: Royal Society of Chemistry Publishing; 2008.
and others Gustafson RF. The Upas tree: Pushkin and Erasmus Darwin. PMLA. 1960;75(1):101–109.
function of the microbiome Dietert RR, Silbergeld EK. Biomarkers for the 21st century: listening to the microbiome. Toxicol Sci. 2015;144(2):208–216.
called xenobiotics Maurice CF, Haiser HJ, Turnbaugh PJ. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell. 2013;152(1–2):39–50; Carmody RN, Turnbaugh PJ. Host-microbial interactions in the metabolism of therapeutic and diet-derived xenobiotics. J Clin Invest. 2014;124(10):4173–4181.
2010 Vancouver Winter Olympics Kurczy S. Lindsey Vonn race suit: how big an advantage at Vancouver Olympics? The Christian Science Monitor. February 26, 2010. http://www.csmonitor.com/World/Olympics/Olympics-blog/2010/0226/Lindsey-Vonn-race-suit-How-big-an-advantage-at-Vancouver-Olympics. Accessed October 10, 2015.
wear them in competition Daily Mail Reporter. Unsuitable: Team USA drop their high-tech speedskating suits after disappointing opening week at the Olymipcs. Mail Online. February 14, 2014. http://www.dailymail.co.uk/news/article-2559755/The-secret-suits-High-tech-speedskating-uniforms-created-space-engineers-main-complaint-shocking-U-S-performance-Sochi.html. Accessed October 10, 2015.
suits and/or equipment Chadwick N. Will success on the ice of Sochi rekindle enthusiasm for an Amsterdam Olympics? The Amsterdam Herald. March 1, 2014. http://www.amsterdamherald.com/index.php/election-2012-blog/1159-20140301-will-success-on-ice-of-sochi-rekindle-enthusiasm-amsterdam-olympics. Accessed October 10, 2015.
three sets of triplets Murphy K, O’Shea CA, Ryan CA, et al. The gut microbiota composition in dichorionic triplet sets suggests a role for host genetic factors. PLoS ONE. 2015;10(4):e0122561. doi:10.1371/journal.pone.0122561.
our puppet, Pinocchio Stilling RM, Dinan TG, Cryan JF. The brain’s Geppetto-microbes as puppeteers of neural function and behaviour? J Neurovirol. 2015. doi:10.1007/S13365-015-0355x.
4. The Incomplete Generation
congenital heart defects Kim JH, Scialli AR. Thalidomide: the tragedy of birth defects and the effective treatment of disease. Toxicol Sci. 2011;122(1):1–6.
sensory challenges Green CR, Roane J, Hewitt A, et al. Frequent behavioural challenges in children with fetal alcohol spectrum disorder: a needs-based assessment reported by caregivers and clinicians. J Popul Ther Clin Pharmacol. 2014;21(3):e405–e420.
“functional ability of the baby” Birth defects: specific birth defects. Centers for Disease Control and Prevention. http://www.cdc.gov/ncbddd/birthdefects/types.html. Accessed July 3, 2015.
physiological changes Birth defects research. The Teratology Society. http://www.teratology.org/index.asp. Accessed July 3, 2015.
degenerative disorders What are the types of birth defects? Eunice Kennedy Shriver National Institute of Child Health and Human Development. NIH. https://www.nichd.nih.gov/health/topics/birthdefects/conditioninfo/Pages/types.aspx. Accessed July 4, 2015.
“how the body works” Birth defects & other health conditions. March of Dimes. http://www.marchofdimes.org/complications/birth-defects-and-health-conditions.aspx. Accessed July 4, 2015.
“environmentally induced” Birth defect. Merriam-Webster. http://www.merriam-webster.com/dictionary/birth%20defect. Accessed July 4, 2015.
several health problems Orme CM, Boyden LM, Choate KA, Antaya RJ, King BA. Capillary malformation—arteriovenous malformation syndrome: review of the literature, proposed diagnostic criteria, and recommendations for management. Pediatr Dermatol. 2013;30(4):409–415. doi:10.1111/pde.12112.
birth defect in the baby Dietert RR. The microbiome in early life: self-completion and microbiota protection as health priorities. Birth Defects Res B Dev Reprod Toxicol. 2014;101(4):333–340.
type of birth defect Dietert RR. The microbiome in early life: self-completion and microbiota protection as health priorities. Birth Defects Res B Dev Reprod Toxicol. 2014;101(4):333–340.
propionic acid MacFabe DF, Cain NE, Boon F, et al. Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: relevance to autism spectrum disorder. Behav Brain Res. 2011;217(1):47–54; MacFabe DF. Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders. Microb Ecol Health Dis. 2012;23:19260; MacFabe DF. The propionic acid rodent model of autism. 2012. Video. Autism Canada. https://vimeo.com/79418104.
risk of autoimmune disease Alenghat T. Epigenomics and the microbiota. Toxicol Pathol. 2015;43(1):101–106; An D, Oh SF, Olszak T, et al. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell. 2014;156(1–2):123–133.
interdisciplinary research team Powell S. Antibiotics, infants and food allergy. University of South Carolina. 2014. http://www.sc.edu/uofsc/posts/2014/07_love_bryan_infant_antibiotics.php#.VoErCbYrKW9. Accessed June 22, 2015.
food allergy epidemic Love B. Food allergies antibiotic exposure. South Carolina College of Pharmacy. 2014. https://www.sccp.sc.edu/content/cpos-research-feature-bryan-love-%E2%80%93-food-allergies-antibiotic-exposure. Accessed September 4, 2015.
leading cause of disability The U.S. government and global non-communicable diseases. Global Health Policy. The Henry J. Kaiser Family Foundation. 2014. http://kff.org/global-health-policy/fact-sheet/the-u-s-government-and-global-non-communicable-diseases/. Accessed June 21, 2015.
their action plans Noncommunicable diseases. Pan American Health Organization. World Health Organization. http://www.paho.org/hq/index.php?option=com_content&view=article&id=771&Itemid=852. Accessed June 21, 2015.
partner initiatives Non communicable diseases and disability: creating synergies, reducing inequalities, advancing development. 2013. NCD Alliance. http://ncdalliance.org/sites/default/files/rfiles/NCDs%20and%20Disability%20Final_0.pdf. Accessed June 21, 2015.
an atypical human body DePoy E, Gilson S. Disability as microcosm: the boundaries of the human body. Societies. 2012;2(4):302–316. doi:10.3390/soc2040302.
from all microbes “Bubble boy” 40 years later: look back at heartbreaking case. CBS News. http://www.cbsnews.com/pictures/bubble-boy-40-years-later-look-back-at-heartbreaking-case/. Accessed July 5, 2015.
virus in the donor cells Stewart DD, Morgenstern J. The Boy in the Plastic Bubble. Movie. 1976. http://www.imdb.com/title/tt0074236/. Accessed July 5, 2015.
requiring many services from others Bebinger M. Troubled future for young adults on autism spectrum. WBUR’s CommonHealth Reform and Reality. 2014. http://commonhealth.wbur.org/2014/06/aging-out-autism-services. Accessed September 4, 2015.
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with Asperger’s syndrome Monsebraaten L. The autism project: York University students with Asperger’s thrive in mentorship program. The Star. November 17, 2012. http://www.thestar.com/news/investigations/2012/11/17/the_autism_project_york_university_students_with_aspergers_thrive_in_mentorship_program.html. Accessed September 4, 2015.
disabled student population Individuals with Disabilities Education Act cost impact on local school districts. Atlas. 2015. http://atlas.newamerica.org/individuals-disabilities-education-act-cost-impact-local-school-districts. Accessed September 4, 2015.
long-term caretakers Stone RI, Wiener JM. Who will care for us? Addressing the long-term care workforce crisis. The Urban Institute. 2001. http://aspe.hhs.gov/basic-report/who-will-care-us-addressing-long-term-care-workforce-crisis. Accessed July 4, 2015.
student services offices Settlement agreement between the United States of America and Lesley University, DJ 202-36-231. January 2013. http://www.ada.gov/lesley_university_sa.htm. Accessed June 21, 2015.
accommodation plans Trotch C. Food for thought: applying the ADA to students with food allergies. Natl Assoc of College and Univ Attorneys. 2014;12(7). http://www.higheredcompliance.org/resources/FoodAllergies.pdf. Accessed June 21, 2015; Grasgreen A. Dining disabilities. Inside Higher Ed. January 2, 2013. https://www.insidehighered.com/news/2013/01/02/lesley-settlement-flags-food-allergies-and-campus-dining. Accessed June 21, 2015.
improper immune maturation Stefka AT, Feehley T, Tripathi P, et al. Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci USA. 2014;111(36):13145–13150.
and wealth Nightingale CH. Segregation: A Global History of Divided Cities. Chicago, IL: University of Chicago Press; 2012; Bishop B. The Big Sort: Why the Clustering of Like-Minded America Is Tearing Us Apart. New York, NY: Houghton Mifflin Harcourt; 2008.
unintentionally increase segregation Antony PJ. Segregation Hurts: Voices of Youth with Disabilities and Their Families in India. Rotterdam, the Netherlands: Sense Publishers; 2013; Gates B, ed. Learning Disabilities: Towards Inclusion. 5th ed. London, England: Churchill Livingstone; 2007.
still a challenge NPR Staff. Learning with disabilities: one effort to shake up the classroom. NPR on WSKG Public Radio. 2014. http://www.npr.org/2014/04/27/307467382/learning-with-disabilities-one-effort-to-shake-up-the-classroom. Accessed June 22, 2015.
5. Gene Swaps and Switches
Corynebacterium diphtheriae Freeman VJ. Studies on the virulence of bacteriophage-infected strains of Corynebacterium diphtheriae. J Bacteriol. 1951;61(6):675–688.
the same viruses Akiba T, Koyama K, Ishiki Y, et al. On the mechanism of the development of multiple-drug-resistant clones of Shigella. Jpn J Microbiol. 1960;4(2):219–227.
occasionally exchange genes Liu L, Chen X, Skogerbø G, et al. The human microbiome: a hot spot of microbial horizontal gene transfer. Genomics. 2012;100(5):265–270.
transfer of genes could occur De la Cruz F, Davies J. Horizontal gene transfer and the origin of species: lessons from bacteria. Trends Microbiol. 2000;8(3):128–133; Salzberg SL, White O, Peterson J, Eisen JA. Microbial genes in the human genome: lateral transfer or gene loss? Science. 2001;292(5523):1903–1906; Kurland CG, Canback B, Berg OG. Horizontal gene transfer: a critical view. Proc Natl Acad Sci USA. 2003;100(17):9658–9662.
demonstrated in 2005 Monroe, D. Jumping genes cross plant species boundaries. PLoS Biol. 2006;4(1):e35. doi:10.1371/journal.pbio.0040035.
unique enzyme activities Crisp A, Boschetti C, Perry M, et al. Expression of multiple horizontally acquired genes is a hallmark of both vertebrate and invertebrate genomes. Genome Biol. 2015;16:50.
control mechanism is a central Crisp A, Boschetti C, Perry M, et al. Expression of multiple horizontally acquired genes is a hallmark of both vertebrate and invertebrate genomes. Genome Biol. 2015;16:50.
epigenetic gene switches Ginder GD. Epigenetic regulation of fetal globin gene expression in adult erythroid cells. Transl Res. 2015;165(1):115–125.
hemoglobin expression Steliou K, Boosalis MS, Perrine SP, et al. Butyrate histone deacetylase inhibitors. Biores Open Access. 2012;1(4):192–198.
beta-thalassemia Bianchi N, Chiarabelli C, Zuccato C, et al. Erythroid differentiation ability of butyric acid analogues: identification of basal chemical structures of new inducers of foetal haemoglobin. Eur J Pharmacol. 2015;752:84–91.
personal book of life Hoffmann A, Zimmermann CA, Spengler D. Molecular epigenetic switches in neurodevelopment in health and disease. Front Behav Neurosci. 2015;9:120. doi:10.3389/fnbeh.2015.00120.
maintenance of memories Zovkic IB, Guzman-Karlsson MC, Sweatt JD. Epigenetic regulation of memory formation and maintenance. Learn Mem. 2013;20(2):61–74.
your immune response van den Elsen PJ, van Eggermond MC, Wierda RJ. Epigenetic control in immune function. Adv Exp Med Biol. 2011;711:36–49. doi:10.1007/978-1-4417-8216-2_4.
responses to those hormones Wojcicka A, Piekielko-Witkowska A, Kedzierska H, et al. Epigenetic regulation of thyroid hormone receptor beta in renal cancer. PLoS ONE. 2014;9(5):e97624. doi:10.1371/journal.pone.0097624; Ouni M, Belot MP, Castell AL, et al. The P2 promoter of the IGF1 gene is a major epigenetic locus for GH responsiveness. Pharmacogenomics J. 2015. doi:10.1038/tpj.2015.26.
quality of sperm production Guerrero-Bosagna C, Savenkova M, Hague MM, et al. Environmentally induced epigenetic transgenerational inheritance of altered Sertoli cell transcriptome and epigenome: molecular etiology of male infertility. PLoS ONE. 2013;8(3):e59922. doi:10.1371/journal.pone.0059922; Meikar O, Da Ros M, Kotaja N. Epigenetic regulation of male germ cell differentiation. Subcell Biochem. 2013;61:119–138.
developing immune system occurs Dietert RR, Dietert J. Strategies for Protecting Your Child’s Immune System. Hackensack, NJ: World Scientific Publishing; 2010; Dietert RR. Developmental immunotoxicity, perinatal programming, and noncommunicable diseases: focus on human studies. Adv Med. 2014. Article ID 867805. doi:10.1155/2014/867805.
absence of key microbes Murgatroyd C, Spengler D. Epigenetics of early child development. Front Psychiatry. 2011;2(16):1–15. doi:10.3389/fpsyt.2011.00016; Godfrey KM, Costello PM, Lillycrop KA. The developmental environment, epigenetic biomarkers and long-term health. J Dev Orig Health Dis. 2015;6(5):399–406; Lillycrop KA, Burdge GC. Maternal diet as a modifier of offspring epigentics. J Dev Orig Health Dis. 2015;6(2):88–95; Zhao Q, Hou J, Chen B, et al. Prenatal cocaine exposure impairs cognitive function of progeny via insulin growth factor II epigenetic regulation. Neurobiol Dis. 2015;82:54–65; Dietert RR. Transgenerational epigenetics of endocrine-disrupting chemicals. In: Tollefsbol T, ed. Transgenerational Epigenetics. San Diego, CA: Elsevier; 2014:239–254; Remely M, Aumueller E, Jahn D, et al. Microbiota and epigenetic regulation of inflammatory mediators in type 2 diabetes and obesity. Benef Microbes. 2014;5(1):33–43; Interlandi J. The toxins that affected your great-grandparents could be in your genes. Smithsonian Magazine. 2013. http://www.smithsonianmag.com/innovation/the-toxins-that-affected-your-great-grandparents-could-be-in-your-genes-180947644/. Accessed July 13, 2015.
maturity as you age Dietert RR, Etzel RA, Chen D, et al. Workshop to identify critical windows of exposure for children’s health: immune and respiratory systems work group summary. Environ Health Perspect. 2000;108(Suppl 3):483–490; Jernigan TL, Baaré WF, Stiles J, Madsen KS. Postnatal brain development: structural imaging of dynamic neurodevelopmental processes. Prog Brain Res. 2011;189:77–92; Harding R, Pinkerton KE, eds. The Lung: Development, Aging and the Environment. 2nd ed. San Diego, CA: Elsevier; 2014.
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Barker hypothesis Paneth N, Susser M. Early origin of coronary heart disease (the “Barker hypothesis”). BMJ. 1995;310(6977):411–412.
later-life disease Fox DA, Lucchini R, Aschner M, et al. Local effects and global impact in neurotoxicity and neurodegeneration: the Xi’an International Neurotoxicology Conference. Neurotoxicology. 2012;33(4):629–630; Walker CL, Ho SM. Developmental reprogramming of cancer susceptibility. Nat Rev Cancer. 2012;12(7):479–486; Heindel JJ, Vandenberg LN. Developmental origins of health and disease: a paradigm for understanding disease cause and prevention. Curr Opin Pediatr. 2015;27(2):248–253; Bousquet J, Anto JM, Berkouk K, et al. Developmental determinants in non-communicable chronic diseases and ageing. Thorax. 2015;70(6):595–597.
and colleagues Crews D, Gillette R, Miller-Crews I, et al. Nature, nurture and epigenetics. Mol Cell Endocrinol. 2014;398(1–2):42–52.
“understanding of biological processes” Crews D, Gillette R, Miller-Crews I, et al. Nature, nurture and epigenetics. Mol Cell Endocrinol. 2014;398(1–2):42–52.
chemicals in mice Skinner MK, Savenkova MI, Zhang B, et al. Gene bionetworks involved in the epigenetic transgenerational inheritance of altered mate preference: environmental epigenetics and evolutionary biology. BMC Genomics. 2014;15:377. doi:10.1186/1471-2164-15-377.
hunger winter Lumey LH, Van Poppel FWA. The Dutch Famine of 1944–45: mortality and morbidity in past and present generations. Soc Hist Med. 1994;7(2):229–246. doi:10.1093/shm/7.2.229.
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diabetes as adults Van Abeelen AF, Elias SG, Bossuyt PM, et al. Famine exposure in the young and the risk of type 2 diabetes in adulthood. Diabetes. 2012;61(9):2255–2260.
general population Veenendaal MV, Painter RC, De Rooij SR, et al. Transgenerational effects of prenatal exposure to the 1944–45 Dutch famine. BJOG. 2013;120(5):548–553.
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our mammalian genes Kumar H, Lund R, Laiho A, et al. Gut microbiota as an epigenetic regulator: pilot study based on whole-genome methylation analysis. MBio. 2014;5(6):e02113-e02114. doi:10.1128/mBio.02113-14; Khan S, Jena G. The role of butyrate, a histone deacetylase inhibitor in diabetes mellitus: experiental evidence for therapeutic intervention. Epigenomics. 2015;7(4):669–680.
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6. Redirecting Precision Medicine
the twenty-first century Jain KK. Personalized medicine. Curr Opin Mol Ther. 2002;4(6):548–558.
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the individual patient National Research Council (US) Committee on a Framework for Developing a New Taxonomy of Disease. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. Washington, DC: National Academies Press; 2011.
electronic health records Precision Medicine in Action. Public Health Genomics. Centers for Disease Control and Prevention. http://www.cdc.gov/genomics/public/features/precision_med.htm. 2015. Accessed September 7, 2015.
a big problem Rubin R. Precision medicine: the future or simply politics? JAMA. 2015;313(11):1089–1091.
next annual visit Dietert RR, Dietert JM. The microbiome and sustainable healthcare. Healthcare. 2015;3(1):100–129. doi:10.3390/healthcare3010100.
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unnecessary tests and referrals Goodman B. Use time with your doctor wisely. Arthritis Foundation. http://www.arthritis.org/living-with-arthritis/health-care/your-health-care-team/doctors-appointment-challenge.php. Accessed September 7, 2015.
7. The Immune System Gone Wrong
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published in early 2010 Dietert RR, Dietert J. Strategies for Protecting Your Child’s Immune System. Hackensack, NJ: World Scientific Publishing; 2010.
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Columbus in the New World Castillo-Rojas G, Cerbón MA, López-Vidal Y. Presence of Helicobacter pylori in a Mexican pre-Columbian mummy. BMC Microbiol. 2008,8:119. doi:10.1186/1471-2180-8-119.
hygiene hypothesis Strachan DP, Taylor EM, Carpenter RG. Family structure, neonatal infection, and hay fever in adolescence. Arch Dis Child 1996;74:422–426. doi:10.1136/adc.74.5.422.
called dendritic cells Amedei A, Codolo G, Del Prete G, et al. The effect of Heliobacter pylori on asthma and allergy. J. Asthma Allergy. 2010;3:139–147. doi:10.2147/JAA.S8971; Oertli M, Müller A. Helicobacter pylori targets dendritic cells to induce immune tolerance, promote persistence and confer protection against allergic asthma. Gut Microbes. 2012;3(6):566–571; Oertli M, Sundquist M, Hitzler I, et al. DC-derived Il-18 drives treg differentiation, murine Helicobacter pylori-specific immune tolerance, and asthma protection. J Clin Invest. 2012;122(3):1082–1096; Arnold IC, Dehzad N, Reuter S, et al. Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells. J Clin Invest. 2011;121(8):3088–3093; Arnold IC, Hitzler I, Müller A. The immunomodulatory properties of Helicobacter pylori confer protection against allergic and chronic inflammatory disorders. Front Cell Infect Microbiol. 2012;16(2):10. doi:10.3389/fcimb.2012.00010; Engler DB, Loenardi I, Hartung ML, et al. Helicobacter pylori-specific protection against inflammatory bowel disease requires the NLRP3 inflammasome and IL-18. Inflamm Bowel Dis. 2015;21(4):854–861.
way to produce disease Heller F, Fuss IJ, Nieuwenhuis EE, et al. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity. 2002;17(5):629–638.
human ulcerative colitis Fuss IJ, Strober W. The role of IL-13 and NK T cells in experimental and human ulcerative colitis. Mucosal Immunol. 2008;1(Suppl 1):S31–S3.
avoid later-life disease An D, Oh SF, Olszak T, et al. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell. 2014; 156(1–2):123–133; Olszak T, An D, Zeissig S, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science. 2012;336(6080):489–493; Erturk-Hasdemir D, Kasper DL. Resident commensals shaping immunity. Curr Opin Immunol. 2013;25(4):450–455.
approximately 675,000 in the United States The pandemic: influenza strikes. United States Department of Health and Human Services. http://www.flu.gov/pandemic/history/1918/the_pandemic/influenza/. Accessed September 7, 2015.
aberrant inflammatory response The pandemic: influenza strikes. United States Department of Health and Human Services. http://www.flu.gov/pandemic/history/1918/the_pandemic/influenza. Accessed July 18, 2015; Morens DM, Fauci AS. The 1918 influenza pandemic: insights for the 21st century. J Infect Dis. 2007;195(7):1018–1028. doi:10.1086/511989.
among healthy young adults Morens DM, Fauci AS. The 1918 influenza pandemic: insights for the 21st century. J Infect Dis. 2007;195(7):1018–1028; Morens DM, Taubenberger JK, Harvey HA, Memoli MJ. The 1918 influenza pandemic: lessons for 2009 and the future. Crit Care Med. 2010;38(Suppl 4):e10–e20.
Fatal Sequence: The Killer Within Tracey KJ. Fatal Sequence: The Killer Within. Chicago, IL: University of Chicago Press; 2005.
8. Patterns of Disease
population were overweight Obesity and overweight. Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/fastats/obesity-overweight.htm. Accessed September 9, 2015.
one-third of the population NCHS Health E-Stat. Prevalence of overweight, obesity and extreme obesity among adults: United States, trends 1960–62 through 2005–2006. Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/data/hestat/overweight/overweight_adult.htm. Accessed September 9, 2015.
children were obese Obesity and overweight. Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/fastats/obesity-overweight.htm. Accessed September 9, 2015.
pro-inflammatory condition Scarpellini E, Tack J. Obesity and metabolic syndrome: an inflammatory condition. Dig Dis. 2012;30(2):148–153; Olson S. Obesity’s link to inflammation may unlock a switch responsible for bad fat. Med Daily. February 19, 2015. http://www.medicaldaily.com/obesitys-link-inflammation-may-unlock-switch-responsible-bad-fat-322692. Accessed September 9, 2015.
diseases like cancer Howe LR, Subbaramaiah K, Hudis CA, Dannenberg A J. Molecular pathways: adipose inflammation as a mediator of obesity-associated cancer. Clin Cancer Res. 2013;19(22):6074–6083.
different types of cancer Schauer P, Chand B. Reducing obesity-related comorbidities through bariatric surgery. Bariatrics Today. 2006;3. https://my.clevelandclinic.org/ccf/media/files/Bariatric_Surgery/rccoe.pdf. Accessed September 10, 2015; Mayo Clinic Staff. Complications. Diseases and conditions: obesity. Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/obesity/basics/complications/con-20014834. Accessed September 10, 2015; Lalwani AK, Katz K, Liu YH, et al. Obesity is associated with sensorineural hearing loss in adolescents. Laryngoscope. 2013;123(12):3178–3184; Kumar S, Han J, Li T, Qureshi AA. Obesity, waist circumference, weight change and the risk of psoriasis in US women. J Eur Acad Dermatol Venereol. 2013;27(10):1293–1298; Chuang YF, An Y, Bilgel M, et al. Midlife adiposity predicts earlier onset of Alzheimer’s dementia, neuropathology and presymptomatic cerebral amyloid accumulation. Mol Psychiatry. 2015; Pauli-Pott U, Neidhard J, Heinzel-Gutenbrunner M, Becker K. On the link between attention deficit/hyperactivity disorder and obesity: do comorbid oppositional defiant and conduct disorder matter? Eur Child Adolesc Psychiatry. 2014;23(7):531–537; Qin B, Yang M, Fu H, et al. Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis. Arthritis Res Ther. 2015;17(1):86; Gianfrancesco MA, Acuna B, Shen L, et al. Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors. Obes Res Clin Pract. 2014;8(5):e435–e447; Behrens G, Matthews CE, Moore SC, et al. Body size and physical activity in relation to incidence of chronic obstructive pulmonary disease. CMAJ. 2014;186(12):e457–e469; Hall ME, do Carmo JM, da Silva AA, et al. Obesity, hypertension, and chronic kidney disease. Int J Nephrol Renovasc Dis. 2014;7:75–88. doi:10.2147/IJNRD.S39739.
buildup can occur slowly Hilgendorf I, Swirski FK, Robbins CS. Monocyte fate in atherosclerosis. Arterioscler Thromb Vasc Biol. 2015;35(2):272–279.
infant decades earlier Hoffman M. Atherosclerosis: your arteries age by age. Hardening of the arteries starts earlier than you may think. Heart Disease Health Center. WebMD. http://www.webmd.com/heart-disease/features/atherosclerosis-your-arteries-age-by-age. Accessed July 25, 2015; Kelishadi R. Inflammation-induced atherosclerosis as a target for prevention of cardiovascular diseases from early life. Open Cardiovasc Med J. 2010;4:24–29. doi: 10.2174/1874192401004020024.
atherosclerosis will occur Kelishadi R. Inflammation-induced atherosclerosis as a target for prevention of cardiovascular diseases from early life. Open Cardiovasc Med J. 2010;4:24–29. doi:10.2174/1874192401004020024; Labayen I, Ortega FB, Sjöström M, Ruiz JR. Early life origins of low-grade inflammation and atherosclerosis risk in children and adolescents. J Pediatr. 2009;155(5):673–677.
unhealthy inflammation Kataoka Y, Puri R, Nicholls SJ. Inflammation, plaque progression and vulnerability: evidence from intravascular ultrasound imaging. Cardiovasc Diagn Ther. 2015;5(4):280–289.
risk of atherosclerosis Chistiakov DA, Bobryshev YV, Kozarov E, et al. Role of gut microbiota in the modulation of atherosclerosis-associated immune response. Front Microbiol. 2015;6:671. doi:10.3389/fmicb.2015.00671.
lose tissue function Ogura S, Shimosawa T. Oxidative stress and organ damages. Curr Hypertens Rep. 2014;16(8):452.
cells become cancerous Chew SH, Toyokuni S. Malignant mesothelioma as an oxidative stress-induced cancer: an update. Free Radic Biol Med. 2015;86:166–178.
strep throat Tan SY, Dee MK. Elie Metchnikoff (1845–1916): discoverer of phagocytosis. Singapore Med J. 2009:50(5):456–457. http://www.pasteur.fr/infosci/biblio/ressources/histoire/textes_integraux/metchnikoff/smjmetabio2009tan.pdf. Accessed September 8, 2015.
Alzheimer’s disease, and diabetes Leading causes of death. Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Accessed July 25, 2015.
prescription medication Stone K. The most prescribed medications by drug class. About.com. http://pharma.about.com/od/Sales_and_Marketing/a/The-Most-Prescribed-Medications-By-Drug-Class.htm. Accessed July 25, 2015.
being overweight Dietert RR, DeWitt JC, Germolec DR, Zelikoff JT. Breaking patterns of environmentally influenced disease for health risk reduction: immune perspectives. Environ Health Perspect. 2010;118(8):1091–1099. doi:10.1289/ehp.1001971.
other autoimmune conditions Kollipara S. Comorbidities associated with type I Diabetes. NASN School Nurse. 2010;25(1)19–21; Franzese A, Mozzillo E, Nugnes R, et al. Type 1 diabetes mellitus and co-morbidities. In: Wagner D, ed. Type 1 Diabetes Complications. InTech; 2011. doi:10.5772/24457. Available from: http://www.intechopen.com/books/type-1-diabetes-complications/type-1-diabetes-mellitus-and-co-morbidities. Accessed July 24, 2015; Farsani SF, Souverein PC, van der Vorst MMJ, et al. Chronic comorbidities in children with type I diabetes: a population-based cohort study. Arch Dis Child. 2015;100(8):763–768. doi:10.1136/archdischild-2014-307654; Butwicka A, Frisén L, Almqvist C, et al. Risks of psychiatric disorders and suicide attempts in children and adolescents with type I diabetes: a population-based cohort study. Diabetes Care. 2015;38(3):453–459.
associations with type 1 diabetes Harding JL, Shaw JE, Peeters A, et al. Cancer risk among people with type I and type 2 diabetes: disentangling true associations, detection bias, and reverse causation. Diabetes Care. 2015;38(2):264–270.
and type 1 diabetes Lauret E, Rodrigo L. Celiac disease and autoimmune-associated conditions. Biomed Res Int. 2013. Article ID 127589. doi:10.1155/2013/127589.
small bowel adenocarcinoma Dietert RR. Inflammatory bowel disease and celiac disease: environmental risks factors and consequences. In: Dietert RR, Luebke RW, eds. Immunotoxicity, Immune Dysfunction, and Chronic Disease. New York, NY: Humana Press, 2012:Chapter 12; Wagner G, Zeiler M, Berger G, et al. Eating disorders in adolescents with celiac disease: influence of personality characteristics and coping. Eur Eat Disorders Rev. 2015;23(5). doi:10.1002/erv.2376; Thompson JS, Lebwohl B, Reilly NR, et al. Increased incidence of eosinophilic esophagitis in children and adults with celiac disease. J Clin Gastroenterol. 2012;46(1):e6–e11.
resistant to treatment Blackmon K, Bluvstein J, MacAllister WS, et al. Treatment resistant epilepsy in autism spectrum disorder: increased risk for females. Autism Res. 2015. doi:10.1002/aur.1514.
overall population Kang V, Wagner GC, Ming X. Gastrointestinal dysfunction in children with autism spectrum disorders. Autism Res. 2014;7(4):501–506. doi:10.1002/aur.1386.
ASD in children Fadini CC, Lamônica DA, Fett-Conte AC, et al. Influence of sleep disorders on the behavior of individuals with autism spectrum disorder. Front Hum Neurosci. 2015;9:347. doi:10.3389/fnhum.2015.00347.
majority of NCDs Dietert RR, DeWitt JC, Germolec DR, Zelikoff JT. Breaking patterns of environmentally influenced disease for health risk reduction: immune perspectives. Environ Health Perspect. 2010;118(8):1091–1099. doi:10.1289/ehp.1001971.
among ASD children Theoharides TC. Autism spectrum disorders and mastocytosis. Int J Immunopathol Pharmacol. 2009;22(4):859–865.
bipolar disorder Croen LA, Zerbo O, Qian Y, et al. The health status of adults on the autism spectrum. Autism. 2015;19(7):814–823. doi:10.1177/136236131557517.
lead to depression Bay-Richter C, Linderholm KR, Lim CK, et al. A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality. Brain Behav Immun. 2015;43:110–117; De Chant T. Depression may be caused by inflammation. NOVA Next. January 5, 2015. http://www.pbs.org/wgbh/nova/next/body/depression-may-caused-inflammation. Accessed September 9, 2015.
much longer list Vancampfort D, Mitchell AJ, De Hert M, et al. Type 2 diabetes in patients with major depressive disorder: a meta-analysis of prevalence estimates and predictors. Depress Anxiety. 2015;32(10):763–773; Carey M, Small H, Yoong SL, et al. Prevalence of comorbid depression and obesity in general practice: a cross-sectional survey. Br J Gen Pract. 2014;64(620):e122–e127; Dietert RR, DeWitt JC, Luebke RW. Reducing the prevalence of immune-based chronic disease. In: Dietert RR, Luebke RW. eds. Immunotoxicity, Immune Dysfunction, and Chronic Disease, New York, NY: Humana Press, 2012:Chapter 17.
an all-time high Wehrwein P. Astounding increase in antidepressant use by Americans. Harvard Health Publications. Harvard Medical School. October 20, 2011. http://www.health.harvard.edu/blog/astounding-increase-in-antidepressant-use-by-americans-201110203624. Accessed July 29, 2015.
associated with them Machiels K, Joossens M, Sabino J, et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2014;63(8):1275–1283; Lourenço TG, Heller D, Silva-Boghossian CM, et al. Microbial signature profiles of periodontally healthy and diseased patients. J Clin Periodontol. 2014;41(11):1027–1036.
Alzheimer’s disease Zhao Y, Lukiw WJ. Microbiome-generated amyloid and potential impact on amyloidogenesis in Alzheimer’s disease (AD). J Nat Sci. 2015;1(7). pii:e138.
Asthma Huang YJ, Boushey HA. The microbiome in asthma. J Allergy Clin Immunol. 2015;135(1):25–30.
Autism Buie T. Potential etiologic factors of microbiome disruption in autism.Clin Ther. 2015;37(5):976–983.
Autoimmune hepatitis Lin R, Zhou L, Zhang J, Wang B. Abnormal intestinal permeability and microbiota in patients with autoimmune hepatitis. Int J Clin Exp Pathol. 2015;8(5):5153–5160.
Breast cancer Xuan C, Shamonki JM, Chung A, et al. Microbial dysbiosis is associated with human breast cancer. PLoS ONE. 2014;9(1):e83744.doi:10.1371/journal.pone.0083744.
Cardiovascular disease Org E, Mehrabian M, Lusis AJ. Unraveling the environmental and genetic interactions in atherosclerosis: central role of the gut microbiota. Atherosclerosis. 2015;241(2):387–399.
Celiac disease Verdu EF, Galipeau HJ, Jabri B. Novel players in coeliac disease pathogenesis: role of the gut microbiota. Nat Rev Gastroenterol Hepatol. 2015;12(9):497–506.
Chronic kidney disease Montemurno E, Cosola C, Dalfino G, et al. What would you like to eat, Mr CKD Microbiota? A mediterranean diet, please! Kidney Blood Press Res. 2014;39(2–3):114–123.
Chronic obstructive pulmonary disease (COPD) Sze MA, Dimitriu PA, Suzuki M, et al. Host response to the lung microbiome in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2015;192(4):438–445.
Colon cancer Gao Z, Guo B, Gao R, et al. Microbiota disbiosis is associated with colorectal cancer. Front Microbiol. 2015;6:20. doi:10.3389/fmicb.2015.00020.
Crohn’s disease Schaubeck M, Clavel T, Calasan J, et al. Dysbiotic gut microbiota causes transmissible Crohn’s disease-like ileitis independent of failure in antimicrobial defence. Gut. 2015. pii: gutjnl-2015-309333.
Depression Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186–194.
Food allergies Stefka AT, Feehley T, Tripathi P, et al. Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci USA. 2014;111(36):13145–13150.
Hypertension Jose PA, Raj D. Gut microbiota in hypertension. Curr Opin Nephrol Hypertens. 2015;24(5):403–409.
Laryngeal cancer Gong H, Shi Y, Zhou X, et al. Microbiota in the throat and risk factors for laryngeal carcinoma. Appl Environ Microbiol. 2014;80(23):7356–7363.
Lung cancer Hosgood HD 3rd, Sapkota AR, Rothman N, et al. The potential role of lung microbiota in lung cancer attributed to household coal burning exposures. Environ Mol Mutagen. 2014;55(8):643–651.
Lupus Van Praet JT, Donovan E, Vanassche I, et al. Commensal microbiota influence systemic autoimmune responses. EMBO J. 2015;34(4):466–474.
Nonalcoholic fatty liver disease Abdul-Hai A, Abdallah A, Malnick SD. Influence of gut bacteria on development and progression of non-alcoholic fatty liver disease. World J Hepatol. 2015;7(12):1679–1684. doi:10.4254/wjh.v7.i12.1679.
Obesity Tilg H, Adolph TE. Influence of the human intestinal microbiome on obesity and metabolic dysfunction. Curr Opin Pediatr. 2015;27(4):496–501.
Osteoporosis Ohlsson C, Sjögren K. Effects of the gut microbiota on bone mass. Trends Endocrinol Metab. 2015;26(2):69–74.
Parkinson’s disease Keshavarzian A, Green SJ, Engen PA, et al. Colonic bacterial composition in Parkinson’s disease. Mov Disord. 2015;30(10):1351–1360.
Periodontal disease Lourenço TG, Heller D, Silva-Boghossian CM, et al. Microbial signature profiles of periodontally healthy and diseased patients. J Clin Periodontol. 2014;41(11):1027–1036.
Prostate cancer Yu H, Meng H, Zhou F, et al. Urinary microbiota in patients with prostate cancer and benign prostatic hyperplasia. Arch Med Sci. 2015;11(2):385–394.
Psoriasis Scher JU, Ubeda C, Artacho A, et al. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol. 2015;67(1):128–139.
Respiratory allergies Melli LC, do Carmo-Rodrigues MS, Araújo-Filho H, et al. Intestinal microbiota and allergic diseases: a systematic review. Allergol Immunopathol (Madr). 2015. pii: S0301-0546(15)00059-2.
Rheumatoid arthritis Brusca SB, Abramson SB, Scher JU. Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Curr Opin Rheumatol. 2014;26(1):101–107.
Schizophrenia Severance EG, Gressitt KL, Stallings CR, et al. Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia. Schizophr Res. 2013;148(1–3):130–137.
Sudden infant death syndrome (SIDS) Highet AR, Berry AM, Bettelheim KA, Goldwater PN. Gut microbiome in sudden infant death syndrome (SIDS) differs from that in healthy comparison babies and offers an explanation for the risk factor of prone position. Int J Med Microbiol. 2014;304(5–6):735–741.
Type 1 diabetes Alkanani AK, Hara N, Gottlieb PA, et al. Alterations in intestinal microbiota correlate with susceptibility to type 1 diabetes. Diabetes. 2015;64(10):3510–3520.
Type 2 diabetes Upadhyaya S, Banerjee G. Type 2 diabetes and gut microbiome: at the intersection of known and unknown. Gut Microbes. 2015;6(2):85–92.
Ulcerative colitis Lavelle A, Lennon G, O’Sullivan O, et al. Spatial variation of the colonic microbiota in patients with ulcerative colitis and control volunteers. Gut. 2015;64(10):1553–1561.
Urothelial cancer Xu W, Yang L, Lee P, et al. Mini-review: perspective of the microbiome in the pathogenesis of urothelial carcinoma. Am J Clin Exp Urol. 2014;2(1):57–61.
to become obese Duca FA, Sakar Y, Lepage P, et al. Replication of obesity and associated signaling pathways through transfer of microbiota from obese-prone rats. Diabetes. 2014;63(5):1624–1636.
complete microbiome is present Esposito D, Damsud T, Wilson M, et al. Black currant anthocyanins attenuate weight gain and improve glucose metabolism in diet-induced obese mice with intact, but not disrupted, gut microbiome. J Agric Food Chem. 2015;63(27):6172–6180.
altering the microbiome Kim BS, Song MY, Kim H. The anti-obesity effect of Ephedra sinica through modulation of gut microbiota in obese Korean women. J Ethnopharmacol. 2014;152(3):532–539.
treating the condition Gut bacteria may affect whether a statin drug lowers cholesterol. Science News. Science Daily. October 14, 2011. http://www.sciencedaily.com/releases/2011/10/111013184815.htm. Accessed July 25, 2015; Yoo DH, Kim IS, Van Le TK, et al. Gut microbiota-mediated drug interactions between lovastatin and antibiotics. Drug Metab Dispos. 2014;42(9):1508–1513.
digoxin metabolism is compromised Haiser HJ, Seim KL, Balskus EP, Turnbaugh PJ. Mechanistic insight into digoxin inactivation by Eggerthella lenta augments our understanding of its pharmacokinetics. Gut Microbes. 2014;5(2):233–238.
cyclophosphamide chemotherapy Iida N, Dzutsev A, Stewart CA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013;342(6161):967–970; Viaud S, Saccheri F, Mignot G, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342(6161):971–976; Karin M, Jobin C, Balkwill F. Chemotherapy, immunity and microbiota—a new triumvirate? Nat Med. 2014;20(2):126–127.
9. The Six Causes of the Epidemic
US infants and children Chai G, Governale L, McMahon AW, et al. Trends of outpatient prescription drug utilization in US children, 2002–2010. Pediatrics. 2012;130(1):23–31.
tissues and organs Vangay P, Ward T, Gerber JS, Knights D. Antibiotics, pediatric dysbiosis, and disease. Cell Host Microbe. 2015;17(5):553–564; Saari A, Virta LJ, Sankilampi U, et al. Antibiotic exposure in infancy and risk of being overweight in the first 24 months of life. Pediatrics. 2015;135(4):617–626.
complications often occurs Dietert RR, Dietert JM. The microbiome and sustainable healthcare. Healthcare. 2015;3(1):100–129. doi:10.3390/healthcare3010100; Llor C, Bjerrum L. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Ther Adv Drug Saf. 2014;5(6):229–241; Venekamp RP, Sanders S, Glasziou PP, et al. Antibiotics for acute otitis media in children. Cochrane Database Syst Rev. 2013;1:CD000219. doi:10.1002/14651858.CD000219.pub3; Milligan S, McCrery S. Should children with acute otitis media routinely be treated with antibiotics? No: most children older than two years do not require antibiotics. Am Fam Physician. 2013;88(7). Online. Accessed August 5, 2015.
deaths each year Antibiotic resistance threats in the United States, 2013. Centers for Disease Control and Prevention. http://www.cdc.gov/drugresistance/threat-report-2013/. Accessed September 10, 2015.
susceptibility to serious infections Vangay P, Ward T, Gerber JS, Knights D. Antibiotics, pediatric dysbiosis, and disease. Cell Host Microbe. 2015;17(5):553–564.
late 1960s in the UK Dibner JJ, Richards JD. Antibiotic growth promoters in agriculture: history and mode of action. Poult Sci. 2005;84(4):634–643.
via egg injections Strom S. Antibiotics eliminated in hatchery, Perdue says. The New York Times. September 3, 2014. http://www.nytimes.com/2014/09/04/business/perdue-eliminates-antibiotic-use-in-its-hatcheries.html. Accessed September 9, 2015.
among major producers Grow B, Huffstutter PJ. Major poultry farms routinely feed antibiotics to chickens. Huff Post Green. September 15, 2014. http://www.huffingtonpost.com/2014/09/15/poultry-farms-antibiotics-chickens_n_5822438.html. Accessed September 9, 2015.
pathogen load during production Dietert RR, Golemboski KA, Austic RE. Environment-immune interactions. Poult Sci. 1994;73(7):1062–1076.
other media sources Spotts PN. Controlling bacteria on the farm. The Christian Science Monitor. June 25, 1998. http://www.csmonitor.com/1998/0625/062598.feat.feat.7.html. Accessed September 10, 2015.
such as bifidobacteria LeBlanc JG, Milani C, de Giori GS, et al. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol. 2013;24(2):160–168.
westernized diet Sonnenburg ED, Sonnenburg JL. Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell Metab. 2014;20(5):779–786.
different than in the past Cyril S, Oldroyd JC, Renzaho A. Urbanisation, urbanicity, and health: a systematic review of the reliability and validity of urbanicity scales. BMC Public Health. 2013;13:513. doi:10.1186/1471-2458-13-513.
castle from the early 1100s History of Edinburgh Castle. Edinburgh Castle. http://www.edinburghcastle.co.uk/history/. Accessed July 20, 2015.
in the cramped spaces Graham HG. The Social Life of Scotland in the Eighteenth Century. London, England: Adam and Charles Black; 1906.
buildings as possible Life and death in Old Edinburgh. The Edinburgh Dungeon. http://www.thedungeons.com/edinburgh/en/downloads/edinburgh_schools_resource_life_and_death.pdf. Accessed July 21, 2015.
well-respected merchants Fortescue WI. James Ker, member of parliament for Edinburgh, 1747–1754. The Book of the Old Edinburgh Club. 2014;10:17–44.
“unhealthy hovel” Chambers R, Thomson T. A Biographical Dictionary of Eminent Scotsmen (volume 5). Glasgow, Scotland: Blackie; 1854.
healthier housing The Scots Peerage. Paul JB, ed. The Genealogist (volume 2). Exeter, England: William Pollard & Company; 1878; Thomson T. A Biographical Dictionary of Eminent Scotsmen (volume 5). Glasgow, Scotland: Blackie; 1854.
at the time The Scots Peerage. Paul JB, ed. The Genealogist (volume 2) Exeter, England. William Pollard & Company; 1878; Chambers R. Lives of Illustrious and Distinguished Scotsman, Forming a Complete Scottish Biographical Dictionary (volume 3). Glasgow, Scotland: Blackie and Son; 1839.
half of all deaths City of Edinburgh council area—demographic factsheet. National Records of Scotland. http://www.nrscotland.gov.uk/files/statistics/council-area-data-sheets/city-of-edinburgh-factsheet.pdf. Accessed July 20, 2015.
ten million people World’s population increasingly urban with more than half living in urban areas. United Nations Department of Economic and Social Affairs. July 10, 2014. http://www.un.org/en/development/desa/en/news/population/world-urbanization-prospects.html. Accessed July 20, 2015.
most common killer, NCDs Giles-Corti B, Badland H, Mavoa S, et al. Reconnecting urban planning with health: a protocol for the development and validation of national liveability indicators associated with noncommunicable disease risk behaviours and health outcomes. Public Health Res Pract. 2014;25(1). pii: e2511405. doi:10.17061/phrp2511405; Cooper R, Boyko CT, Cooper C. Design for health: the relationship between design and noncommunicable diseases. J Health Commun. 2011;16(Suppl 2):134–157; Smit W, de Lannoy A, Dover RV, et al. Making unhealthy places: The built environment and non-communicable diseases in Khayelitsha, Cape Town. Health Place. 2015;35:11–18.
contributed heavily to the deaths Geronimus AT. To mitigate, resist, or undo: addressing structural influences on the health of urban populations. In: Hynes HP, Lopez R, eds. Urban Health: Readings in the Social, Built, and Physical Environments of U.S. Cities. Sudbury, MA: Jones & Bartlett; 2009.
elevated systemic inflammation Viehmann A, Hertel S, Fuks K, et al. Long-term residential exposure to urban air pollution, and repeated measures of systemic blood markers of inflammation and coagulation. Occup Environ Med. 2015;72(9):656–663.
heart disease and asthma Ghosh R, Lurmann F, Perez L, et al. Near-roadway air pollution and coronary heart disease: burden of disease and potential impact of a greenhouse gas reduction strategy in Southern California. Environ Health Perspect. 2015. doi:10.1289/ehp.1408865; Cesaroni G, Badaloni C, Gariazzo C, et al. Long-term exposure to urban air pollution and mortality in a cohort of more than a million adults in Rome. Environ Health Perspect. 2013;121(3):324–331; Perez L, Declercq C, Iñiguez C, et al. Chronic burden of near-roadway traffic pollution in 10 European cities (APHEKOM network). Eur Respir J. 2013;42(3):594–560; Matsui EC. Environmental exposures and asthma morbidity in children living in urban neighborhoods. Allergy. 2014;69(5):553–558.
air pollution of cities Leon Hsu HH, Mathilda Chiu YH, Coull BA, et al. Prenatal particulate air pollution and asthma onset in urban children. Identifying sensitive windows and sex differences. Am J Respir Crit Care Med. 2015;192(9):1052–1059.
increases the risk of obesity Jerrett M, McConnell R, Wolch J, et al. Traffic-related air pollution and obesity formation in children: a longitudinal, multilevel analysis. Environ Health. 2014;13:49. doi:10.1186/1476-069X-1349; Ponticiello BG, Capozzella A, Di Giorgio V, et al. Overweight and urban pollution: preliminary results. Sci Total Environ. 2015;518–519:61–64.
Canada or Australia Weller C. This Chinese mega-city has more people than Canada or Australia. Business Insider Australia. July 9, 2015. http://www.businessinsider.com.au/chinese-mega-city-has-more-people-than-canada-argentina-or-australia-2015-7. Accessed July 20, 2015.
130 million people Johnson I. Yanjiao: ambitious supercity of 130 million people developing around Beijing. The Economic Times. July 20, 2015. http://economictimes.indiatimes.com/news/international/business/yanjiao-ambitious-supercity-of-130-million-people-developing-around-beijing/articleshow/48142531.cms. Accessed July 20, 2015.
hygiene hypothesis Von Mutius E. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: farm lifestyles and the hygiene hypothesis. Clin Exp Immunol. 2010;160(1):130–135.
risk of multiple NCDs Riedler J, Braun-Fahrländer C, Eder W, et al. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet. 2001;358(9288):1129–1133; Ege MJ, Herzum I, Büchele G, et al. Prenatal exposure to a farm environment modifies atopic sensitization at birth. J Allergy Clin Immunol. 2008;122(2):407–412; Nicolaou N, Siddique N, Custovic A. Allergic disease in urban and rural populations: increasing prevalence with increasing urbanization. Allergy. 2005;60(11):1357–1360; Growing up on a farm directly affects regulation of the immune system, study finds. Science News. Science Daily. February 8, 2012. http://www.sciencedaily.com/releases/2012/02/120208132549.htm. Accessed September 10, 2015; Growing up on livestock farm halves risk of inflammatory bowel diseases. Science News. Science Daily. July 11, 2014. http://www.sciencedaily.com/releases/2014/07/140711101347.htm. Accessed September 10, 2015.
movie version are planned Busch A. “Green Acres” moving from Hooterville to Hollywood. Feature film. Broadway play in the works. Deadline Hollywood. May 2, 2014. http://deadline.com/2014/05/green-acres-movie-broadway-show-722481/. Accessed July 23, 2015.
allergic disease and asthma Von Ehrenstein OS, Von Mutius E, Illi S, et al. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy. 2000;30(2):187–193; Riedler J, Braun-Fahrländer C, Eder W, et al. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet. 2001;358(9288):1129–1133; Von Mutius E, Radon K. Living on a farm: impact on asthma induction and clinical course. Immunol Allergy Clin North Am. 2008;28(3):631–647.
affect immune development Schröder PC, Li J, Wong GW, Schaub B. The rural-urban enigma of allergy: what can we learn from studies around the world? Pediatr Allergy Immunol. 2015;26(2):95–102. doi:10.1111/pai.12341; Lluis A, Depner M, Gaugler B, et al. Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood. J Allergy Clin Immunol. 2014;133(2):551–559; Pfefferle PI, Büchele G, Blümer N, et al. Cord blood cytokines are modulated by maternal farming activities and consumption of farm dairy products during pregnancy: the PASTURE Study. J Allergy Clin Immunol. 2010;125(1):108–115.
would be produced Schuijs MJ, Willart MA, Vergote K, et al. Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science. 2015:349(6252):1106–1110.
noncommunicable diseases Thysen AH, Larsen JM, Rasmussen MA, et al. Prelabor cesarean section bypasses natural immune cell maturation. J Allergy Clin Immunol. 2015;136(4):1123–1125; Mesquita DN, Barbieri MA, Goldani HA, et al. Cesarean section is associated with increased peripheral and central adiposity in young adulthood: cohort study. PLoS ONE. 2013;8(6):e66827. doi:10.1371/journal.pone.0066827; Jakobsson HE, Abrahamsson TR, Jenmalm MC, et al. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut, 2014;63(4):559–566; Dietert RR. Natural childbirth and breastfeeding as preventive measures of immune-microbiome dysbiosis and misregulated inflammation. J Anc Dis Prev Rem. 2013;1(2):103. http://dx.doi.org/10.4172/jadpr1000103.
complementary therapy is used Miniello VL, Colasanto A, Cristofori F, et al. Gut microbiota biomodulators, when the stork comes by the scalpel. Clin Chim Acta. 2015;451(Pt A):88–96. doi:10.1016/j.cca.2015.01.022.
global cesarean deliveries Dietert RR. Natural childbirth and breastfeeding as preventive measures of immune-microbiome dysbiosis and misregulated inflammation. J Anc Dis Prev Rem. 2013;1(2):103. doi:10.4172.jadpr1000103.
dying women who were with child Cesarean section—a brief history, part I. US National Library of Medicine. https://www.nlm.nih.gov/exhibition/cesarean/part1.html. Accessed July 22, 2015.
until the 1580s Cesarean section—a brief history, part I. US National Library of Medicine. https://www.nlm.nih.gov/exhibition/cesarean/part1.html. Accessed July 22, 2015.
between 1996 and 2007 Recent trends in cesarean delivery in the United States. NCHS Data Brief. Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/data/databriefs/db35.htm. Accessed July 22, 2015.
states and ethnic groups Recent trends in cesarean delivery in the United States. NCHS Data Brief. Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/data/databriefs/db35.htm. Accessed July 22, 2015.
years 1997 and 2006 Karlström A, Lindgren H, Hildingsson I. Maternal and infant outcome after caesarean section without recorded medical indication: findings from a Swedish case-control study. BJOG. 2013;120(4):479–486.
between 1990 and 2008 Bragg F, Cromwell DA, Edozien LC, et al. Variation in rates of caesarean section among English NHS trusts after accounting for maternal and clinical risk: cross sectional study. BMJ. 2010:341(7777):c5065. doi:10.1136/bmj.c5065.
England, 24 percent Bragg F, Cromwell DA, Edozien LC, et al. Variation in rates of caesarean section among English NHS trusts after accounting for maternal and clinical risk: cross sectional study. BMJ. 2010;341(7777):c5065.
US, 33 percent Births—method of delivery. FastStats. Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/fastats/delivery.htm. Accessed July 22, 2015.
India, 40 percent Ajeet S, Nandkishore K. The boom in unnecessary caesarean surgeries is jeopardizing women’s health. Health Care Women Int. 2013;34(6):513–521.
country of origin Teixeira C, Correia S, Victora CG, Barros H. The Brazilian preference: cesarean delivery among immigrants in Portugal. PLoS ONE. 2013;8(3):e60168. doi:10.1371/journal.pone.0060168.
China, 46 percent Lumbiganon P, Laopaiboon M, Gülmezoglu AM, et al. Method of delivery and pregnancy outcomes in Asia: the WHO global survey on maternal and perinatal health 2007–08. Lancet. 2010;375(9713):490–499.
first year of life Bäckhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015;17(5):690–703.
“Moms Deliver Twice!” Frese SA, Mills DA. Birth of the infant gut microbiome: moms deliver twice! Cell Host Microbe. 2015;17(5):543–544.
birth by C-section Mastromarino P, Capobianco D, Miccheli A, et al. Administration of a multistrain probiotic product (VSL#3) to women in the perinatal period differentially affects breast milk beneficial microbiota in relation to mode of delivery. Pharmacol Res. 2015;95–96:63–70.
further maturation after birth Dietert RR, Dietert J. Strategies for Protecting Your Child’s Immune System. Hackensack, NJ: World Scientific Publishing; 2010.
suppressed in the infant Jakobsson HE, Abrahamsson TR, Jenmalm MC, et al. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut. 2014;63(4):559–566.
Th1 immune responses Puff R, D’Orlando O, Heninger AK, et al. Compromised immune response in infants at risk for type 1 diabetes born by caesarean section. Clin Immunol. 2015;160(2):282–285.
vaginally delivered children Van Berkel AC, den Dekker HT, Jaddoe VW, et al. Mode of delivery and childhood fractional exhaled nitric oxide, interrupter resistance and asthma: the Generation R study. Pediatr Allergy Immunol. 2015;26(4):330–336.
from vaginal births Sevelsted A, Stokholm J, Bønnelykke K, Bisgaard H. Cesarean section and chronic immune disorders. Pediatrics. 2015;135(1):e92–e98.
obesity Kuhle S, Tong OS, Woolcott CG. Association between caesarean section and childhood obesity: a systematic review and meta-analysis. Obes Rev. 2015;16(4):295–303.
autism spectrum disorders and ADHD Curran EA, O’Neill SM, Cryan JF, et al. Research review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. J Child Psychol Psychiatry. 2015;56(5):500–508.
high blood pressure Horta BL, Gigante DP, Lima RC, et al. Birth by caesarean section and prevalence of risk factors for non-communicable diseases in young adults: a birth cohort study. PLoS ONE. 2013;8(9):e74301. doi:10.1371/journal.pone.0074301.
celiac disease Mårild K, Stephansson O, Montgomery S, et al. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study. Gastroenterology. 2012;142(1):39–45.
risk of food allergies Koplin J, Allen K, Gurrin L, et al. Is caesarean delivery associated with sensitization to food allergens and IgE-mediated food allergy: a systematic review. Pediatr Allergy Immunol. 2008;19(8):682–687.
atopic dermatitis Lee SY, Yu J, Ahn KM, et al. Additive effect between IL-13 polymorphism and cesarean section delivery/prenatal antibiotics use on atopic dermatitis: a birth cohort study (COCOA). PLoS ONE. 2014;9(5):e96603.
serious birth defects Fintel B, Samaras TS, Carias E. The thalidomide tragedy: lessons for drug safety and regulation. HELIX. July 28, 2009. https://helix.northwestern.edu/article/thalidomide-tragedy-lessons-drug-safety-and-regulation. Accessed July 23, 2015.
major health hazard Asbestos health effects. ATSDR. http://www.atsdr.cdc.gov/asbestos/asbestos/health_effects/. Accessed July 23, 2015.
exposed children Lanphear BP, Hornung R, Khoury J, et al. Low-level environmental lead exposure and children’s intellectual function: an international pooled analysis. Environ Health Perspect. 2005;113(7): 894-899; Wells EM, Bonfield TL, Dearborn DG, Jackson LW. The relationship of blood lead with immunoglobulin E, eosinophils, and asthma among children: NHANES 2005–2006. Int J Hyg Environ Health. 2014;217(2–3):196–204.
numerous physiological systems Menard S, Guzylack-Piriou L, Leveque M, et al. Food intolerance at adulthood after perinatal exposure to the endocrine disruptor bisphenol A. FASEB J. 2014;28(11):4893–4900; Strakovsky RS, Wang H, Engeseth NJ, et al. Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis. Toxicol Appl Pharmacol. 2015;284(2):101–112; Mileva G, Baker SL, Konkle ATM, Bielajew C. Bisphenol-A: epigenetic reprogramming and effects on reproduction and behavior. Int J Environ Res Public Health. 2014;11(7):7537–7561.
toxicity and cancer Gross L. Flame retardants in consumer products are linked to health and cognitive problems. The Washington Post. April 15, 2013. https://www.washingtonpost.com/national/health-science/flame-retardants-in-consumer-products-are-linked-to-health-and-cognitive-problems/2013/04/15/f5c7b2aa-8b34-11e2-9838-d62f083ba93f_story.html. Accessed July 23, 2015.
Legally Poisoned Cranor CF. Legally Poisoned: How the Law Puts Us at Risk from Toxicants. Cambridge, MA: Harvard University Press; 2011.
food emulsifiers Chassaing B, Koren O, Goodrich JK, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015;519(7541):92–96.
following some surgeries Kastl KG, Betz CS, Siedek V, Leunig A. Effect of carboxymethylcellulose nasal packing on wound healing after functional endoscopic sinus surgery. Am J Rhinol Allergy. 2009;23(1):80–84.
including Lactobacillus species Clair E, Linn L, Travert C, et al. Effects of Roundup(®) and glyphosate on three food microorganisms: Geotrichum candidum, Lactococcus lactis subsp. cremoris and Lactobacillus delbrueckii subsp. bulgaricus. Curr Microbiol. 2012;64(5):486–491; Shehata AA, Kühnert M, Haufe S, Krüger M. Neutralization of the antimicrobial effect of glyphosate by humic acid in vitro. Chemosphere. 2014;104:258–261.
10. Precision Medicine Envisaged
“Medicine’s Next Frontier” Tirrell M. Medicine’s next frontier: the microbiome. CNBC. Biotech and Pharmaceuticals. June 19, 2015. http://www.cnbc.com/2015/06/19/medicines-next-frontier-the-microbiome.html. Accessed July 28, 2015.
available hospital bugs House L. Would you “seed” your baby? The surprising post-birth trend on the rise that sees mothers who have c-sections bathe newborns in vaginal fluid. Mail Online. June 24, 2015. http://www.dailymail.co.uk/femail/article-3136832/Would-seed-baby-alarming-post-birth-trend-rise-Australia-sees-mothers-C-sections-bathe-newborns-vaginal-fluid.html. Accessed September 10, 2015.
diversity in human milk Cabrera-Rubio R, Collado MC, Laitinen K, et al. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr. 2012;96(3):544–551.
neuroactive compounds Wall R, Cryan JF, Ross RP, et al. Bacterial neuroactive compounds produced by psychobiotics. Adv Exp Med Biol. 2014;817:221–239.
the drug Prozac Kantak PA, Bobrow DN, Nyby JG. Obsessive-compulsive-like behaviors in house mice are attenuated by a probiotic (Lactobacillus rhamnosus GG). Behav Pharmacol. 2014;25(1):71–79.
pharmaceutical-based therapies Mohammadi AA, Jazayeri S, Khosravi-Darani K, et al. The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: a randomized, double-blind, placebo-controlled trial in petrochemical workers. Nutr Neurosci. 2015. doi:10.1179/1476830515Y.0000000023.
these treatments work Nelson MH, Diven MA, Huff LW, Paulos CM. Harnessing the microbiome to enhance cancer immunotherapy. J Immunol Res. 2015;2015:Article ID368736.
production of butyrate Ohashi Y, Sumitani K, Tokunaga M, et al. Consumption of partially hydrolysed guar gum stimulates Bifidobacteria and butyrate-producing bacteria in the human large intestine. Benef Microbes. 2015;6(4):451–455.
food more efficiently Pruszynska-Oszmalek E, Kolodziejski PA, Stadnicka K, et al. In ovo injection of prebiotics and synbiotics affects the digestive potency of the pancreas in growing chickens. Poult Sci. 2015;94(8):1909–1916.
fight against NCDs Sharon G, Garg N, Debelius J, et al. Specialized metabolites from the microbiome in health and disease. Cell Metab. 2014;20(5):719–730.
fewer complications Vicari E, La Vignera S, Castiglione R, et al. Chronic bacterial prostatitis and irritable bowel syndrome: effectiveness of treatment with rifaximin followed by the probiotic VSL#3. Asian J Androl. 2014;16(5):735–739.
produce allergies Giacomin P, Croese J, Krause L, et al. Suppression of inflammation by helminths: a role for the gut microbiota? Philos Trans R Soc Lond B Biol Sci. 2015;370(1675). pii: 20140296; Afifi MA, Jiman-Fatani AA, El Saadany S, Fouad MA. Parasites–allergy paradox: disease mediators or therapeutic modulators. J Microscopy and Ultrastruct. 2015;3(2):53–61.
compared with controls Dhiman RK, Rana B, Agrawal S, et al. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology. 2014;147(6):1327–1337.
autoimmune disease Mardini HE, Grigorian AY. Probiotic mix VSL#3 is effective adjunctive therapy for mild to moderately active ulcerative colitis: a meta-analysis. Inflamm Bowel Dis. 2014;20(9):1562–1567.
heart disease Sanaie S, Ebrahimi-Mameghani M, Mahmoodpoor A, et al. Effect of a probiotic preparation (VSL#3) on cardiovascular risk parameters in critically-ill patients. J Cardiovasc Thorac Res. 2013;5(2):67–70.
liver disease in children Miccheli A, Capuani G, Marini F, et al. Urinary (1)H-NMR-based metabolic profiling of children with NAFLD undergoing VSL#3 treatment. Int J Obes. 2015;39(7):1118–1125.
irritable bowel syndrome Wong RK, Yang C, Song GH, et al. Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: a randomized double-blinded placebo study. Dig Dis Sci. 2015;60(1):186–194.
responses to food allergens Cosenza L, Nocerino R, Di Scala C, et al. Bugs for atopy: the Lactobacillus rhamnosus GG strategy for food allergy prevention and treatment in children. Benef Microbes. 2015;6(2):225–232.
3.6 percent of controls Tang MK, Ponsonby AL, Orsini F, et al. Administration of a probiotic with peanut oral immunotherapy: a randomized trial. J Allergy Clin Immunol. 2015;135(3):737–744.
supporting the arthritis Vaghef-Mehrabany E, Alipour B, Homayouni-Rad A, et al. Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis. Nutrition. 2014;30(4):430–435.
overweight/obese adults Dao MC, Everard A, Aron-Wisnewsky J, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. June 22, 2015. pii: gutjnl-2014-308778.
problematic microbes Easton J. Fecal “transplant” helps one-year-old beat relentless infection. Science Life. January 2, 2013. http://sciencelife.uchospitals.edu/2013/01/02/fecal-transplant-helps-one-year-old-beat-relentless-infection/. Accessed July 28, 2015; Kahn SA, Young S, Rubin DT. Colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection in a child. Am J Gastroenterol. 2012;107(12):1930–1931.
colonoscopy procedure Patel NC, Griesbach CL, DiBaise JK, Orenstein R. Fecal microbiota transplant for recurrent Clostridium difficile infection: Mayo Clinic in Arizona experience. Mayo Clin Proc. 2013;88(8):799–805.
90 percent cure rate Orally delivered microbial therapy has potential beyond CDI. Clinical Updates. Mayo Clinic. http://www.mayoclinic.org/medical-professionals/clinical-updates/digestive-diseases/orally-delivered-microbial-therapy-has-potential-beyond-cdi. Accessed July 30, 2015.
capsules taken orally Youngster I, Russell GH, Pindar C, et al. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014;312(17):1772–1778.
the donated poop Moayyedi P, Surette MG, Kim PT, et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology. 2015;149(1):102–109; Hays B. Fecal transplants used successfully to treat ulcerative colitis. UPI. July 3, 2015. http://www.upi.com/Health_News/2015/07/03/Fecal-transplants-used-successfully-to-treat-ulcerative-colitis/8371435935830/. Accessed July 20, 2015; Berman J. Inflammatory bowel disease “cured” with fecal transplant. Voice of America. January 22, 2015. http://www.voanews.com/content/inflammatory-bowel-disease-cured-with-fecal-transplant/2609711.html. Accessed July 30, 2015.
multiple sclerosis Surana NK, Kasper DL. The yin yang of bacterial polysaccharides: lessons learned from B. fragilis PSA. Immunol Rev. 2012;245(1):13–26.
neurodegenerative conditions MacFabe DF. Enteric short-chain fatty acids: microbial messengers of metabolism, mitochondria, and mind: implications in autism spectrum disorders. Microb Ecol Health Dis. 2015;26:28177; Valvassori SS, Varela RB, Arent CO, et al. Sodium butyrate functions as an antidepressant and improves cognition with enhanced neurotrophic expression in models of maternal deprivation and chronic mild stress. Curr Neurovasc Res. 2014;11(4):359–366; Sharma S, Taliyan R, Singh S. Beneficial effects of sodium butyrate in 6-OHDA induced neurotoxicity and behavioral abnormalities: modulation of histone deacetylase activity. Behav Brain Res. 2015;291:306–314.
microbiome-based therapeutics Fukami H, Tachimoto H, Kishi M, et al. Acetic acid bacterial lipids improve cognitive function in dementia model rats. J Agric Food Chem. 2010;58(7):4084-4089.
11. You, the Volatile Organic Compound
chemical tribromoanisole 2,4,6-Tribromoanisole (TBA) Programs. Pharma Resource Group Inc. http://www.pharmarg.com/tribromoanisole.html. Accessed November 13, 2015.
certain amino acids Brennan J. More than just “blue”: the world’s top 10 smelly cheeses. Fine Dining Lovers. October 2, 2012. https://www.finedininglovers.com/stories/blue-cheese-list-smelly-cheeses/. Accessed July 31, 2015; Sourabié AM, Spinnler HE, Bourdat-Deschamps M, et al. S-methyl thioesters are produced from fatty acids and branched-chain amino acids by brevibacteria: focus on L-leucine catabolic pathway and identification of acyl-CoA intermediates. Appl Microbiol Biotechnol. 2012;93(4):1673–1683.
thousand different VOCs “Sniffer” to unlock secrets of chocolate. The Press (New Zealand). September 21, 2008. http://www.stuff.co.nz/the-press/637889/Sniffer-to-unlock-secrets-of-chocolate. Accessed July 31, 2015.
aroma and taste Gupta C, Prakash D, Gupta S. A biotechnological approach to microbially based perfumes and flavours. J Microbiol Exp. 2015;2(1):00034. doi:10.15406/jmen.2015.01.00034.
can readily detect Estapé N. Perfume: why does it smell different on each person? The Healthy Skin Blog. January 17, 2013. http://www.thehealthyskinblog.org/perfume-why-does-it-smell-different-on-each-person/. Accessed August 1, 2015.
repair the epithelial barrier Geirnaert A, Steyaert A, Eeckhaut V, et al. Butyricicoccus pullicaecorum, a butyrate producer with probiotic potential, is intrinsically tolerant to stomach and small intestine conditions. Anaerobe. 2014;30:70-74; Eeckhaut V, Machiels K, Perrier C, et al. Butyricicoccus pullicaecorum in inflammatory bowel disease. Gut. 2013;62(12):1745–1752.
ten parts per million Butyric acid, a very smelly molecule. The Chronicle Flask. November 29, 2014. https://thechronicleflask.wordpress.com/2014/11/29/butyric-acid-a-very-smelly-molecule/. Accessed July 31, 2015.
pee-mails and nosebooks Gadbois S, Reeve C. Canine olfaction: scent, sign, and situation. In: Horowitz A, ed. Domestic Dog Cognition and Behavior. Berlin, Germany: Springer-Verlag; 2014:3–29.
life-threatening situation Frequently asked questions about medical assistance & diabetic alert dogs. Dogs4Diabetics, Inc. http://www.dogs4diabetics.com/about-us/faq/. Accessed July 30, 2015.
signature of the disease Sonoda H, Kohnoe S, Yamazato T, et al. Colorectal cancer screening with odour material by canine scent detection. Gut. 2011;60:814–819.
lung and breast cancers McCulloch M, Jezierski T, Broffman M, et al. Diagnostic accuracy of canine scent detection in early- and late-stage lung and breast cancers. Integr Cancer Ther. 2006;5(1):30–39.
ovarian cancers Horvath G, Järverud GA, Järverud S, Horváth I. Human ovarian carcinomas detected by specific odor. Integr Cancer Ther. 2008;7(2):76–80.
bladder cancer Willis CM, Britton LE, Harris R, et al. Volatile organic compounds as biomarkers of bladder cancer: sensitivity and specificity using trained sniffer dogs. Cancer Biomark. 2010–2011;8(3):145–153.
lower concentrations Butyric acid, a very smelly molecule. The Chronicle Flask. November 29, 2014. https://thechronicleflask.wordpress.com/2014/11/29/butyric-acid-a-very-smelly-molecule/. Accessed July 31, 2015.
mold, based on scent Kauhanen E, Harri M, Nevalainen A, Nevalainen T. Validity of detection of microbial growth in buildings by trained dogs. Environ Int. 2002;28(3):153–157.
instruments can detect it Bomers MK, van Agtmael MA, Luik H, et al. Using a dog’s superior olfactory sensitivity to identify Clostridium difficile in stools and patients: proof of principle study. BMJ. 2012;345:e7396.
over long distances Chiacchia K. Search-and-rescue dogs function and deployment. Allegheny Mountain Rescue Group. http://www.amrg.info/canine-sar/become-a-sar-dog-handler/16-canine-sar/canine-sar/24-search-and-rescue-dogs-function-and-deployment. Accessed August 2, 2015.
water-quality remediation Van De Werfhorst LC, Murray JL, Reynolds S, et al. Canine scent detection and microbial source tracking of human waste contamination in storm drains. Water Environ Res. 2014;86(6):550–558.
correct the problem Van De Werfhorst LC, Murray JL, Reynolds S, et al. Canine scent detection and microbial source tracking of human waste contamination in storm drains. Water Environ Res. 2014;86(6):550–558; Jensen M. Bacteria sniffing canines help track sources of contamination in Kirkland’s Juanita Creek and Seattle’s Thornton Creek. Kirkland Patch. May 5, 2014. http://patch.com/washington/kirkland/bacteria-sniffing-canines-help-track-sources-of-contamination-in-kirklands-juanita-creek-and-seattles-thornton-creek. Accessed August 5, 2015.
causes tuberculosis Giant rats to sniff out tuberculosis. New Scientist. December 15, 2003. https://www.newscientist.com/article/dn4488-giant-rats-to-sniff-out-tuberculosis/. Accessed August 1, 2015.
fart-focused papers Swift N. The adventures of M.D. Levitt, M.D. Annals of Improbable Res. 2006;12(3):26.
autism spectrum disorder Singh K, Connors SL, Macklin EA, et al. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Nat Acad Sci. 2014;111(43):15550–15555.
completely odorless Shelly WB, et al. Axillary odor: experimental study of the role of bacteria, apocrine sweat, and deodorants. AMA Arch Derm Syphilol. 1953;68(3):430–446.
personal microbial cloud Algar J. Your own personal germ cloud: how your microbes follow you around. Tech Times. August 29, 2014. http://www.techtimes.com/articles/14373/20140829/your-own-personal-germ-cloud-how-your-microbes-follow-you-around.htm. Accessed August 2, 2015; Lax S, Smith DP, Hampton-Marcell J, et al. Longitudinal analysis of microbial interaction between humans and the indoor environment. Science. 2014;345(6200):1048–1052.
just other people Campbell C, Gries R, Kashkin G, Gries G. Organosulphur constituents in garlic oil elicit antennal and behavioural responses from the yellow fever mosquito. J Appl Entomol. 2011;135(5):374–381.
skin microbiome Verhulst NO, Qiu YT, Beijleveld H, et al. Composition of human skin microbiota affects attractiveness to malaria mosquitoes. PLoS ONE. 2011;6(12):e28991. doi:10.1371/journal.pone.0028991.
details of the skin microbiome Bouslimani A, Porto C, Rath CM, et al. Molecular cartography of the human skin surface in 3D. Proc Natl Acad Sci USA. 2015;112(17):e2120–e2129.
our co-partners Bouslimani A, Porto C, Rath CM, et al. Molecular cartography of the human skin surface in 3D. Proc Natl Acad Sci USA. 2015;112(17):e2120–e2129.
oils on the skin Cooks RG, Jarmusch AK, Ferreira CR, Pirro V. Skin molecule maps using mass spectrometry. Proc Natl Acad Sci USA. 2015;112(17):5261–5262.
natural deodorants Troccaz M, Gaïa N, Beccucci S, et al. Mapping axillary microbiota responsible for body odours using a culture-independent approach. Microbiome. 2015;3(1):3. doi:10.1186/S40168-014-0064-3.
artificial sweat Callewaert C, Buysschaert B, Vossen E, et al. Artificial sweat composition to grow and sustain a mixed human axillary microbiome. J Microbiol Methods. 2014;103:6–8.
environment of your mouth Zaura E, Mira A. Editorial: the oral microbiome in an ecological perspective. Front Cell Infect Microbiol. 2015;5:39. doi:10.3389/fcimb.2015.00039.
caused by your oral microbes Oral chroma: aiming to set the standard in halitosis measuring devices. Abimedical. http://www.abimedical.com/en/medical/product_01.html. Accessed August 1, 2015.
white wine grapes Muñoz-González C, Cueva C, Ángeles Pozo-Bayón M, Moreno-Arribas MV. Ability of human oral microbiota to produce wine odorant aglycones from odourless grape glycosidic aroma precursors. Food Chem. 2015;187:112–119.
aromatic compounds Piombino P, Genovese A, Esposito S, et al. Saliva from obese individuals suppresses the release of aroma compounds from wine. PLoS ONE. 2014;9(1):e85611. doi:10.1371/journal.pone.0085611.
periodontal disease Allaker RP. Investigations into the micro-ecology of oral malodour in man and companion animals. J Breath Res. 2010;4(1):017103.
many of these changes Stumpf RM, Wilson BA, Rivera A, et al. The primate vaginal microbiome: comparative context and implications for human health and disease. Am J Phys Anthropol. 2013;152(Suppl S57):119–134.
dysfunctional vaginal microbes Ravel J, Brotman RM, Gajer P, et al. Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis. Microbiome. 2013;1(1):29. doi:10.1186/2049-2618-1-29.
microbes within the vagina Nikolaitchouk N. The Female Genital Tract Microbiota: Composition, Relation to Innate Immune Factors, and Effects of Contraceptives. Vastra Frolunda, Sweden: University of Gothenburg; 2009. https://gupea.ub.gu.se/bitstream/2077/20102/1/gupea_2077_20102_1.pdf. Accessed August 2, 2015; Nelson DB, Bellamy S, Odibo A, et al. Vaginal symptoms and bacterial vaginosis (BV): how useful is self-report? Development of a screening tool for predicting BV status. Epidemiol Infect. 2007;135(8):1369–1375.
menstrual period Chaban B, Links MG, Jayaprakash TP, et al. Characterization of the vaginal microbiota of healthy Canadian women through the menstrual cycle. Microbiome. 2014;2:23. doi:10.1168/2049-2618-2-23.
changes in scent Srinivasan S, Fredricks DN. The human vaginal bacterial biota and bacterial vaginosis. Interdiscip Perspect Infect Dis. 2008;2008:750479. doi:10.1155.2008/750479.
phase of the menstrual cycle Cerda-Molina AL, Hernández-López L, de la O CE, et al. Changes in men’s salivary testosterone and cortisol levels, and in sexual desire after smelling female axillary and vulvar scents. Front Endocrinol (Lausanne). 2013;4:159. doi:10.3389/fendo.2013.00159.
complexity and in smaller numbers Vence T. Parsing the penis microbiome. The Scientist. May 29, 2014. http://www.the-scientist.com/?articles.view/articleNo/40092/title/Parsing-the-Penis-Microbiome/. Accessed August 2, 2015.
their sexual activity Yandell K. Circumcision alters the penis microbiome. The Scientist. April 18, 2013. http://www.the-scientist.com/?articles.view/articleNo/35145/title/Circumcision-Alters-the-Penis-Microbiome/. Accessed August 2, 2015.
microbiome as well Vence T. Parsing the penis microbiome. The Scientist. May 29, 2014. http://www.the-scientist.com/?articles.view/articleNo/40092/title/Parsing-the-Penis-Microbiome/. Accessed August 2, 2015.
bacterial vaginosis in women Fishy smell around penis: causes and solutions. Health Anxiety & Panic Headquarters Symptoms Explained by Doctors. http://www.scarysymptoms.com/2012/01/fishy-smell-around-penis-causes-and.html. Accessed August 2, 2015.
human armpit odor Wongchoosuk C, Lutz M, Kerdcharoen T. Detection and classification of human body odor using an electronic nose. Sensors (Basel). 2009;9(9):7234–7249. doi:10.3390/S90907234.
exhaled air Bach JP, Gold M, Mengel D, et al. Measuring compounds in exhaled air to detect Alzheimer’s disease and Parkinson’s disease. PLoS ONE. 2015;10(7):e0132227. doi:10.1871/journal.pone.0132227.
detect cancer De Meij TG, Larbi IB, van der Schee MP, et al. Electronic nose can discriminate colorectal carcinoma and advanced adenomas by fecal volatile biomarker analysis: proof of principle study. Int J Cancer. 2014;134(5):1132–1138.
rather than later Arasaradnam RP, Covington JA, Harmston C, Nwokolo CU. Review article: next generation diagnostic modalities in gastroenterology—gas phase volatile compound biomarker detection. Aliment Pharmacol Ther. 2014;39(8):780–789.
just odor detection Pluznick JL, Protzko RJ, Gevorgyan H, et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci USA. 2013;110(11):4410–4415.
scents as anything else Svoboda E. Scents and sensibility. Psychology Today. January 1, 2008. https://www.psychologytoday.com/articles/200801/scents-and-sensibility. Accessed August 1, 2015.
immune response capabilities Svoboda E. Scents and sensibility. Psychology Today. January 1, 2008. https://www.psychologytoday.com/articles/200801/scents-and-sensibility. Accessed August 1, 2015.
MHC Bolnick DI, Snowberg LK, Caporaso JG, et al. Major histocompatibility complex class IIb polymorphism influences gut microbiota composition and diversity. Mol Ecol. 2014;23(19):4831–4845.
Human Scent Evidence Prada PA, Curran AM, Furton KG. Human Scent Evidence. Boca Raton, FL: CRC Press; 2014.
HLA type Lin P, Bach M, Asquith M, et al. HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats. PLoS ONE. 2014;9(8):e105684. doi:10.1371/journal.pone.0105684.
12. Superorganism Makeover
or Ruminococcus Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–180.
mucins and sugars Keim B. Gut-bacteria mapping finds three global varieties. WIRED. April 20, 2011. http://www.wired.com/2011/04/gut-bacteria-types/. Accessed Aug. 2, 2015; Bushman FD, Lewis JD, Wu GD. Diet, gut enterotypes and health: is there a link? Nestle Nutr Inst Workshop Ser. 2013;77:65–73.
the other by Prevotella Lim MY, Rho M, Song YM, et al. Stability of gut enterotypes in Korean monozygotic twins and their association with biomarkers and diet. Sci Rep. 2014;4:7348. doi:10.1038/srep07348.
clusters of gut microbes Knights D, Ward TL, McKinlay CE, et al. Rethinking “enterotypes.” Cell Host Microbe. 2014;16(4):433–437.
can improve health Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506–514.
gastrointestinal disease Ritchie ML, Romanuk TN. A meta-analysis of probiotic efficacy for gastrointestinal diseases. PLoS ONE. 2012;7(4):e34938. doi:10.1071/journal.pone.0034938; Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506–514.
Gastroenterology & Hepatology Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506–514.
from other animals Chung H, Pamp SJ, Hill JA, et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell. 2012;149(7):1578–1593.
your microbes Kolho KL, Korpela K, Jaakkola T, et al. Fecal microbiota in pediatric inflammatory bowel disease and its relation to inflammation. Am J Gastroenterol. 2015;110(6):921–930; Yang T, Santisteban MM, Rodriguez V, et al. Gut dysbiosis is linked to hypertension. Hypertension. 2015;65(6):1331–1340; Huang YJ, Nariya S, Harris JM, et al. The airway microbiome in patients with severe asthma: associations with disease features and severity. J Allergy Clin Immunol. 2015;136(4):874–884.
proton pump inhibitors Marlicz W, Loniewski I, Grimes DS, Quigley EM. Nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and gastrointestinal injury: contrasting interactions in the stomach and small intestine. Mayo Clin Proc. 2014;89(12):1699–1709.
certain gut bacteria Gut bacteria may affect whether a statin drug lowers cholesterol. Science News. Science Daily. October 14, 2011. http://www.sciencedaily.com/releases/2011/10/111013184815.htm. Accessed August 3, 2015.
adverse drug effects Björklund M, Ouwehand AC, Forssten SD, et al. Gut microbiota of healthy elderly NSAID users is selectively modified with the administration of Lactobacillus acidophilus NCFM and lactitol. Age (Dordr). 2012;34(4):987–999.
affected food preferences Ursell LK, Knight R. Xenobiotics and the human gut microbiome: metatranscriptomics reveal the active players. Cell Metab. 2013;17(3):317–318. doi:10.1016/j.cmet.2013.02.013; McNulty NP, Yatsunenko T, Hsiao A, et al. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins. Sci Transl Med. 2011;3(106):106ra106.
effectiveness considerably German JB. The future of yogurt: scientific and regulatory needs. Am J Clin Nutr. 2014;99(5 Suppl):1271S–1278S.
reproductive tract Kumar N, Behera B, Sagiri SS, et al. Bacterial vaginosis: etiology and modalities of treatment—a brief note. J Pharm Bioallied Sci. 2011;3(4):496–503.
topical application Vaughn AR, Sivamani RK. Effects of fermented dairy products on skin: a systematic review. J Altern Complement Med. 2015;21(7):380–385.
inhibiting periodontal disease Terai T, Okumura T, Imai S, et al. Screening of probiotic candidates in human oral bacteria for the prevention of dental disease. PLoS ONE. 2015;10(6):e0128657. doi:10.1371/journal.pone.0128657.
prevention and therapeutics Zemanick ET, Sagel SD, Harris JK. The airway microbiome in cystic fibrosis and implications for treatment. Curr Opin Pediatr. 2011;23(3):319–324.
real internal struggle Festi D, Schiumerini R, Eusebi LH, et al. Gut microbiota and metabolic syndrome. World J Gastroenterol. 2014;20(43):16079–16094.
the Nurmi concept Nurmi E, Rantala M. New aspects of Salmonella infection in broiler production. Nature. 1973;241(5386):210–211.
specific prebiotic feeding Patterson JA, Burkholder KM. Application of prebiotics and probiotics in poultry production. Poult Sci. 2003;82(4):627–631.
good option Wolfenden AD, Pixley CM, Higgins JP, et al. Evaluation of spray application of a Lactobacillus-based probiotic on Salmonella enteritidis colonization in broiler chickens. Int J Poult Sci. 2007;6(7):493–496.
birds’ microbiome Schneitz C. Competitive exclusion in poultry—30 years of research. Food Control. 2005;16(8):657–667.
under management stress Direct-fed microbials (probiotics) in calf diets. A BAMN Publication. Bovine Alliance on Management and Nutrition. http://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/bamn/BAMN11_Probiotics.pdf. Accessed August 5, 2015.
from gaining a foothold Zhang WH, Jiang Y, Zhu QF, et al. Sodium butyrate maintains growth performance by regulating the immune response in broiler chickens. Br Poult Sci. 2011;52(3):292–301; Fang CL, Sun H, Wu J, et al. Effects of sodium butyrate on growth performance, haematological and immunological characteristics of weanling piglets. J. Anim Physiol Anim Nutr. 2014;98(4):680–685.
skewed as well Honneffer JB, Minamoto Y, Suchodolski JS. Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs. World J Gastroenterol. 2014;20(44):16489–16497; Suchodolski JS, Dowd SE, Wilke V, et al. 16S rRNA gene pyrosequencing reveals bacterial dysbiosis in the duodenum of dogs with idiopathic inflammatory bowel disease. PLoS ONE. 2012;7(6):e39333. doi:10.1371/journal.pone.0039333; Rodrigues Hoffmann A, Patterson AP, Diesel A, et al. The skin microbiome in healthy and allergic dogs. PLoS ONE. 2014;9(1):e83197. doi:10.1371/journal.pone.0083197.
diseases in dogs Strompfová V, Plachá I, Čobanová K, et al. Experimental addition of Eleutherococcus senticosus and probiotic to the canine diet. Cent Eur J Biol. 2012;7(3):436–447.
therapy, and standard care Grześkowiak Ł, Endo A, Beasley S, Salminen S. Microbiota and probiotics in canine and feline welfare. Anaerobe. 2015;34:14–23.
infections in pets Raditic DM. Complementary and integrative therapies for lower urinary tract diseases. Vet Clin North Am Small Anim Pract. 2015;45(4):857–878.
bowel disease in dogs Rossi G, Pengo G, Caldin M, et al. Comparison of microbiological, histological, and immunomodulatory parameters in response to treatment with either combination therapy with prednisone and metronidazole or probiotic VSL#3 strains in dogs with idiopathic inflammatory bowel disease. PLoS ONE. 2014;9(4):e94699. doi:10.1371/journal.pone.0094699.
inflammatory bowel disease Rossi G, Pengo G, Caldin M, et al. Comparison of microbiological, histological, and immunomodulatory parameters in response to treatment with either combination therapy with prednisone and metronidazole or probiotic VSL#3 strains in dogs with idiopathic inflammatory bowel disease. PLoS ONE. 2014;9(4):e94699. doi:10.1371/journal.pone.0094699.
healthy versus sick cats Suchodolski JS, Foster ML, Sohail MU, et al. The fecal microbiome in cats with diarrhea. PLoS ONE. 2015;10(5):e0127378. doi:10.1371/journal.pone.0127378.
renal diseases Cook AK. How to manage feline chronic diarrhea, part II: treatment. DVM 360. July 1, 2010. http://veterinarymedicine.dvm360.com/how-manage-feline-chronic-diarrhea-part-ii-treatment. Accessed August 4, 2015; Levy D. The use of probiotics in cats with renal failure. The Nest. http://pets.thenest.com/use-probiotics-cats-renal-failure-11104.html. Accessed August 4, 2015.
disease in cats Inflammatory bowel disease. Cornell University College of Veterinary Medicine. The Feline Health Center. http://www.vet.cornell.edu/fhc/health_information/brochure_ibd.cfm. Accessed August 4, 2015.
rhamnosus, and salivarius Accepted claims about the nature of probiotic microorganisms in food. Health Canada. April 2009. http://www.hc-sc.gc.ca/fn-an/label-etiquet/claims-reclam/probiotics_claims-allegations_probiotiques-eng.php. Accessed August 4, 2015.
13. To Be a Microbiome Whisperer
need to coexist Cani PD, Everard A. Talking microbes: when gut bacteria interact with diet and host organs. Mol Nutr Food Res. 2015. doi:10.1002/mnfr.201500406.
with healthy controls Abrahamsson TR, Jakobsson HE, Andersson AF, et al. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy. 2014;44(6):842–850; Scher JU, Ubeda C, Artacho A, et al. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol. 2015;67(1):128–139; Shankar V, Hamilton MJ, Khoruts A, et al. Species and genus level resolution analysis of gut microbiota in Clostridium difficile patients following fecal microbiota transplantation. Microbiome. 2014;2(1):13. doi:10.1186/2049-2618-2-13; Hullar MA, Lampe JW. The gut microbiome and obesity. Nestle Nutr Inst Workshop Ser. 2012;73:67–79.
group of humans Clemente JC, Pehrsson EC, Blaser MJ, et al. The microbiome of uncontacted Amerindians. Sci Adv. 2015;1(3). pii: e1500183. doi:10.1126/sciadv.1500183.
infectious diseases Hurtado AM, Lambourne CA, James P, et al. Human rights, biomedical science, and infectious diseases among South American indigenous groups. Annu Rev Anthropol. 2005;34(1):639–665; Hames R, Kuzara J. The nexus of Yanomamö growth, health and demography. In: Salzano FM, Magdalena Hurtado A, eds. Lost Paradises and the Ethics of Research and Publication. New York, NY: Oxford University Press; 2003:Chapter 7.
contact with outsiders Goering L. Invasion of gold miners threat to Brazilian tribe. Chicago Tribune. September 3, 1996. http://articles.chicagotribune.com/1996-09-03/news/9609030156_1_miners-yanomami-land-brazilian-tribe. Accessed September 14, 2015.
in recent decades Mancilha-Carvalho Jde J, Souza e Silva NA. The Yanomami Indians in the INTERSALT study. Arq Bras Cardiol. 2003:80(3):289–300; Manchila-Carvalho JJ, Crews DE. Lipid profiles of Yanomamo Indians of Brazil. Prev Med. 1990;19(1):66–75.
westernized lifestyle Hidalgo G, Marini E, Sanchez W, et al. The nutrition transition in the Venezuelan Amazonia: increased overweight and obesity with transculturation. Am J Human Biol. 2014;26(5):710–712.
gastrointestinal cancers Kahouli I, Tomaro-Duchesneau C, Prakash S. Probiotics in colorectal cancer (CRC) with emphasis on mechanisms of action and current perspectives. J Med Microbiol. 2013; 62(Pt 8):1107–1123.
patient prognosis Mima K, Nishihara R, Qian ZR, et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut. 2015. pii: gutjnl-2015-310101.
gut microbes overall Gao Z, Guo B, Gao R, et al. Probiotics modify human intestinal mucosa-associated microbiota in patients with colorectal cancer. Mol Med Rep. 2015;12(4):6119–6127.
countries in Asia Nakayama J, Watanabe K, Jiang J, et al. Diversity in gut bacterial community of school-age children in Asia. Sci Rep. 2015;5:8397.
counterparts in Bangkok Ruengsomwong S, Korenori Y, Sakamoto N, et al. Senior Thai fecal microbiota comparison between vegetarians and non-vegetarians using PCR-DGGE and real-time PCR. J Microbiol Biotechnol. 2014;24(8):1026–1033.
in the northeast La-Ongkham O, Nakphaichit M, Leelavatcharamas V, et al. Distinct gut microbiota of healthy children from two different geographic regions of Thailand. Arch Microbiol. 2015;197(4):561–573.
features of the microbiome Kemppainen KM, Ardissone AN, Davis-Richardson AG, et al. Early childhood gut microbiomes show strong geographic differences among subjects at high risk for type 1 diabetes. Diabetes Care. 2015;38(2):329–332.
Germany, and Africa Li J, Quinque D, Horz HP, et al. Comparative analysis of the human saliva microbiome from different climate zones: Alaska, Germany, and Africa. BMC Microbiol. 2014;14:316. doi:10.1186/S12866-014-0316-1.
increases significantly Rutherford ST, Bassler BL. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med. 2012;2(11). pii: a012427. doi:10.1101/cshperspect.a012427.
study from the Netherlands Sturme MH, Francke C, Siezen RJ, et al. Making sense of quorum sensing in lactobacilli: a special focus on Lactobacillus plantarum WCFS1. Microbiology. 2007;153(Pt 12):3939–3947.
At least one study Viswanathan VK. Sensing bacteria, without bitterness? Gut Microbes. 2013;4(2):91–93.
microbiome management LaSarre B, Federle MJ. Exploiting quorum sensing to confuse bacterial pathogens. Microbiol Mol Biol Rev. 2013;77(1):73–111.
enzyme called acylase Ivanova K, Fernandes MM, Mendoza E, Tzanov T. Enzyme multilayer coatings inhibit Pseudomonas aeruginosa biofilm formation on urinary catheters. Appl Microbiol Biotechnol. 2015;99(10):4373–4385.
microbes within us Aggarwal C, Jimenez JC, Lee H, et al. Identification of quorum-sensing inhibitors disrupting signaling between Rgg and short hydrophobic peptides in Streptococci. MBio. 2015;6(3):e00393–15. doi:10.1128/mBio.00393-15.
an intriguing study Hsiao A, Ahmed AM, Subramanian S, et al. Members of the human gut microbiota involved in recovery from Vibrio cholerae infection. Nature. 2014;515(7527):423–426.
subvert their functions Barrangou R, Horvath P. The CRISPR system protects microbes against phages, plasmids. Microbe. 2009;4(5):224–230.
Centre for Infection Research Doudna JA, Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science. 2014;346(6213):1258096.
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capacity of memory Virus-cutting enzyme helps bacteria remember a threat. Science News. February 20, 2015. http://newswire.rockefeller.edu/2015/02/20/virus-cutting-enzyme-helps-bacteria-remember-a-threat/. Accessed August 6, 2015.
intact virus attack Hynes AP, Villion M, Moineau S. Adaptation in bacterial CRISPR-Cas immunity can be driven by defective phages. Nat Commun. 2014;5:4399. doi:10.1038/ncomms5399.
host bacterial genome Paez-Espino D, Morovic W, Sun CL, et al. Strong bias in the bacterial CRISPR elements that confer immunity to phage. Nat Commun. 2013;4:1430. doi:10.1038/ncomms2440.
area of the chromosome Levy A, Goren MG, Yosef I, et al. CRISPR adaptation biases explain preference for acquisition of foreign DNA. Nature. 2015;520(7548):505–510.
cell envelope physiology Ratner HK, Sampson TR, Weiss DS. I can see CRISPR now, even when phage are gone: a view on alternative CRISPR-Cas functions from the prokaryotic envelope. Curr Opin Infect Dis. 2015;28(3):267–274.
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14. Your Brain on Microbes
running the world Jensen T. Democrats and Republicans differ on conspiracy theory beliefs. Public Policy Polling. April 2, 2013. http://www.publicpolicypolling.com/pdf/2011/PPP_Release_National_ConspiracyTheories_040213.pdf. Accessed August 11, 2015.
short-chain fatty acids Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015;63:1–9.
parasites and pathogens Stilling RM, Dinan TG, Cryan JF. The brain’s Geppetto-microbes as puppeteers of neural function and behaviour? J Neurovirol. 2015. doi:10.1007/s13365-015-0355-x.
serotonin levels Jackson AC. Diabolical effects of rabies encephalitis. J Neurovirol. 2015. doi:10.1007/s13365-015-0351-1.
microbe’s intent Stilling RM, Dinan TG, Cryan JF. The brain’s Geppetto-microbes as puppeteers of neural function and behaviour? J Neurovirol. 2015. doi: 10.1007/s13365-015-0355-x.
“second brain” Hadhazy A. Think twice: how the gut’s “second brain” influences mood and well-being. Scientific American. February 12, 2010. http://www.scientificamerican.com/article/gut-second-brain/. Accessed August 11, 2015.
as described in Part One Stilling RM, Bordenstein SR, Dinan TG, Cryan JF. Friends with social benefits: host-microbe interactions as a driver of brain evolution and development? Front Cell Infect Microbiol. 2014;4:147. http://dx.doi.org/10.3389/fcimbi2014.00147.
do precisely that Alcock J, Maley CC, Aktipis CA. Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. BioEssays. 2014;36(10):940–949.
preventing NCDs Manach C, Scalbert A, Morand C, et al. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;79(5):727–747.
these chemicals, too Cardona F, Andrés-Lacueva C, Tulipan, S, et al. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem. 2013;24(8):1415–1422.
metabolites in their urine Alcock J. Maley CC, Aktipis CA. Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. BioEssays. 2014;36(10): 940–949; Rezzi S, Ramadan Z, Martin FP, et al. Human metabolic phenotypes link directly to specific dietary preferences in healthy individuals. J Proteome Res. 2007;6(11):4469–4477.
biomarker for obesity De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA. 2010;107(33):14691–14696.
higher B-to-F ratio Norris V, Molina F, Gewirtz AT. Hypothesis: bacteria control host appetites. J Bacteriol. 2013;195(3):411–416.
crave dietary fiber Alcock J, Maley CC, Aktipis CA. Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. BioEssays. 2014;36(10):940–949.
precisely what they want Norris V, Molina F, Gewirtz AT. Hypothesis: bacteria control host appetites. J Bacteriol. 2013;195(3):411–416.
from the gut to the liver Lyte M. Microbial endocrinology: host-microbiota neuroendocrine interactions influencing brain and behavior. Gut Microbes. 2014;5(3):381–389.
and additional bacteria Lyte M. Microbial endocrinology: host-microbiota neuroendocrine interactions influencing brain and behavior. Gut Microbes. 2014;5(3):381–389; Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015;63:1–9; Thomas CM, Hong T, van Pijkeren JP, et al. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS ONE. 2012;7(2):e31951. doi:10.1371/journal.pone.0031951.
bladder control Hadhazy A. Think twice: how the gut’s “second brain” influences mood and well-being. Scientific American. February 12, 2010. http://www.scientificamerican.com/article/gut-second-brain/. Accessed August 11, 2015; Berger M, Gray JA, Roth BL. The expanded biology of serotonin. Annu Rev Med. 2009;60:355–366.
gut bacteria produce Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264–276; Ridaura V, Belkaid Y. Gut microbiota: the link to your second brain. Cell. 2015;161(2):193–194.
behavioral characteristics Stilling RM, Dinan TG, Cryan JF. Microbial genes, brain & behaviour—epigenetic regulation of the gut-brain axis. Genes Brain Behav. 2014;13(1):69–86; Borre YE, Moloney RD, Clarke G, et al. The impact of microbiota on brain and behavior: mechanisms & therapeutic potential. Adv Exp Med Biol. 2014;817:373–403.
connected to neurobehavior Stilling RM, Ryan FJ, Hoban AE, et al. Microbes & neurodevelopment—absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala. Brain Behav Immun. 2015;50:209–220.
social cognition Desbonnet L, Clarke G, Shanahan F, et al. Microbiota is essential for social development in the mouse. Mol Psychiatry. 2014;19(2):146–148.
microbes between individuals Stilling RM, Bordenstein SR, Dinan TG, Cryan JF. Friends with social benefits: host-microbe interactions as a driver of brain evolution and development? Front Cell Infect Microbiol. 2014 ;4:147.
include our microbes Dinan TG, Stilling RM, Stanton C, Cryan, JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015;63:1–9.
cognitive deficits Desbonnet L, Clarke G, Traplin A, et al. Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour. Brain Behav Immun. 2015;48:165–173.
autistic children Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015;63:1–9.
central-nervous-system inflammation Galland L. The gut microbiome and the brain. J Med Food. 2014;17(12):1261–1272.
reduce systemic inflammation Groeger D, O’Mahony L, Murphy EF, et al. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. 2013;4(4):325–339.
June 2014 Brooks M. Top 10 most prescribed, top-selling drugs. Medscape Medical News, WebMD. August 5, 2014. http://www.webmd.com/news/20140805/top-10-drugs. Accessed August 13, 2015.
suicide in the young Aripiprazole. MedlinePlus. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a603012.html. Accessed August 17, 2015.
rose by double digits Pritchard C, Rosenorn-Lanng E. Neurological deaths of American adults (55–74) and the over 75’s by sex compared with 20 Western countries 1989–2010: cause for concern. Surg Neurol Int. 2015;6:123.
another dementia 2015 Alzheimer’s disease facts and figures. Alzheimer’s Assocation. http://www.alz.org/facts/. Accessed August 14, 2015.
autism spectrum disorder Centers for Disease Control and Prevention. March 27, 2014. http://www.gov/nchs/data/nhsr/nhsr087.pdf. Accessed November 18, 2015.
$247 billion each year Children’s mental health—new report. Centers for Disease Control and Prevention. http://www.cdc.gov/features/childrensmentalhealth/. Accessed August 14, 2015.
differ between strains Savignac HM, Tramullas M, Kiely B, et al. Bifidobacteria modulate cognitive processes in an anxious mouse strain. Behav Brain Res. 2015;287:59–72.
antianxiety action in mice Savignac HM, Kiely B, Dinan TG, Cryan JF. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil. 2014;26(11):1615–1627.
stressed students Langkamp-Henken B, Rowe CC, Ford AL, et al. Bifidobacterium bifidum R0071 results in a greater proportion of healthy days and a lower percentage of academically stressed students reporting a day of cold/flu: a randomised, double-blind, placebo-controlled study. Br J Nutr. 2015;113(3):426–434. doi:10.1017/S0007114514003997.
reduced social anxiety Hilimire MR, DeVylder JE, Forestell CA. Fermented foods, neuroticism, and social anxiety: an interaction model. Psychiatry Res. 2015;228(2):203–208.
compared with controls Mohammadi AA, Jazayeri S, Khosravi-Darani K, et al. The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: a randomized, double-blind, placebo-controlled trial in petrochemical workers. Nutr Neurosci. April 16, 2015. doi:10.1179/1476830515Y.0000000023.
needed metabolites Tarr AJ, Galley JD, Fisher SE, et al. The prebiotics 3’Sialyllactose and 6’Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: evidence for effects on the gut-brain axis. Brain Behav Immun. 2015;50:166–177.
Bifidobacterium longum Yu ZT, Chen C, Newburg DS. Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes. Glycobiology. 2013;23(11):1281–1292.
poststress behavioral testing Tarr AJ, Galley JD, Fisher SE, et al. The prebiotics 3’Sialyllactose and 6’Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: evidence for effects on the gut-brain axis. Brain Behav Immun. 2015;50:166–177.
attention and focus Schmidt K, Cowen PJ, Harmer CJ, et al. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl). 2015;232(10):1793–1801.
supplemented formulas Vandenplas Y, Zakharova I, Dmitrieva Y. Oligosaccharides in infant formula: more evidence to validate the role of prebiotics. Br J Nutr. 2015;113(9):1339–1344.
prevalence of colic Giovannini M, Verduci E, Gregori D, et al. Prebiotic effect of an infant formula supplemented with galacto-oligosaccharides: randomized multicenter trial. J Am Coll Nutr. 2014;33(5):385–393.
the hippocampus Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J. Psychiatr Res. 2015;63:1–9.
15. Will You Do No Harm?
risk of NCDs Bisphenol A (BPA). National Institute of Environmental Health Sciences. https://www.niehs.nih.gov/health/topics/agents/sya-bpa/. Accessed August 8, 2015; Toxicological profile for Bisphenol A. California Environmental Protection Agency. September 2009. http://www.opc.ca.gov/webmaster/ftp/project_pages/MarineDebris_OEHHA_ToxProfiles/Bisphenol%20A%20Final.pdf. Accessed August 8, 2015.
to our immune system Braniste V, Jouault A, Gaultier E, et al. Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats. Proc Natl Acad Sci USA. 2010;107(1):448–453.
life stage, infancy Bisphenol A: EU ban on baby bottles to enter into force tomorrow. European Commission. January 2011. http://europa.eu/rapid/press-release_IP-11-664_en.htm. Accessed August 8, 2015.
much consumer protest Summary of bisphenol A (BPA) regulation (2nd edition). Modern Testing Services. May 29, 2013. http://www.mts-global.com/en/technical_update/CPIE-018-13.html. Accessed August 8, 2015; Walsh B. Why the FDA hasn’t banned potentially toxic BPA (yet). Time. April 3, 2012. http://content.time.com/time/health/article/0,8599,2110902,00.html. Accessed August 8, 2015.
and who lags Environment. European Union. http://europa.eu/pol/env/index_en.htm. Accessed August 8, 2015.
inflammation-driven obesity Food additives alter gut microbes, cause diseases in mice. NIH Research Matters. March 16, 2015. http://www.nih.gov/news-events/nih-research-matters/food-additives-alter-gut-microbes-cause-diseases-mice. Accessed August 8, 2015.
biological plausibility are clear Food additives alter gut microbes, cause diseases in mice. NIH Research Matters. March 16, 2015. http://www.nih.gov/news-events/nih-research-matters/food-additives-alter-gut-microbes-cause-diseases-mice. Accessed August 8, 2015.
interactions are extensive Wilson ID, Nicholson JK. The modulation of drug efficacy and toxicity by the gut microbiome. In: Kochhar S, Martin F-P, eds. Metabonomics and Gut Microbiota in Nutrition and Disease. New York, NY: Humana Press; 2015.
true in the US Myhr AI. The precautionary principle in GMO regulations. In: Traavic T, Ching LL, eds. Biosafety First. Trondheim, Norway: Tapir Academic; 2007:Chapter 29; Germany joins ranks of anti-GMO countries. EurActiv.com. April 15, 2009. http://www.euractiv.com/cap/germany-joins-ranks-anti-gmo-cou-news-221725. Accessed August 17, 2015.
types of biofilms Lima IS, Baumeier NC, Rosa RT, et al. Influence of glyphosate in planktonic and biofilm growth of Pseudomonas aeruginosa. Braz J Microbiol. 2014;45(3):971–975.
support foraging animals Druille M, Cabello MN, Garcia Parisi PA, et al. Glyphosate vulnerability explains changes in root-symbionts propagules viability in pampean grasslands. Agric Ecosys Environ 2015;202:48–55. doi:10.1016/j.agee.2014.12.017.
pathogenic to humans Kurenbachk B, Marjoshi D, Amábile-Cuevas CF, et al. Sublethal exposure to commercial formulations of the herbicides dicamba, 2,4-dichlorophenoxyacetic acid, and glyphosate cause changes in antibiotic susceptibility in Escherichia coli and Salmonella enterica serovar typhimurium. mBio. 2015;6(2):e00009–15. doi:10.1128mBio.00009-15.
helpful commensal bacteria Shehata AA, Schrödl W, Aldin AA, et al. The effect of glyphosate on potential pathogens and beneficial members of poultry microbiota in vitro. Curr Microbiol. 2013;66(4):350–358.
Clostridium botulinum Schrödl W, Krüger S, Konstantinova-Müller T, et al. Possible effects of glyphosate on Mucorales abundance in the rumen of dairy cows in Germany. Curr Microbiol. 2014;69(6):817–823; Ackermann W, Coenen M, Schrödl W, et al. The influence of glyphosate on the microbiota and production of botulinum neurotoxin during ruminal fermentation. Curr Microbiol. 2015;70(3):374–382; Krüger M, Shehata AA, Schrödl W, Rodloff A. Glyphosate suppresses the antagonistic effect of Enterococcus spp. on Clostridium botulinum. Anaerobe. 2013;20:74–78.
the FDA handles them Venugopalan V, Shriner KA, Wong-Beringer A. Regulatory oversight and safety of probiotic use. Emerg Infect Dis. 2010:16(11). http://wwwnc.cdc.gov/eid/article/16/11/10-0574_article. Accessed August 10, 2015.
any medical use Lactobacillus acidophilus. University of Maryland Medical Center. https://umm.edu/health/medical/altmed/supplement/lactobacillus-acidophilus. Accessed August 10, 2015.
company shut down FDA: DDS probiotic products seized. FDA News Release. FDA. June 7, 2011. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm258155.htm. Accessed August 10, 2015.
good healthy food Bubnov RV, Spivak MY, Lazarenko LM, et al. Probiotics and immunity: provisional role for personalized diets and disease prevention. EPMA J. 2015;6(1):14.
offer one option Mueller NT, Bakacs E, Combellick J, et al. The infant microbiome development: mom matters. Trends Mol Med. 2015;21(2):109–117.
shift your microbiome Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012;10(10):1096–1100; Venkatesh M, Mukherjee S, Wang H, et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity. 2014;41(2):296–310.
predominant group Mathur R, Barlow GM. Obesity and the microbiome. Expert Rev Gastroenterol Hepatol. 2015;9(8):1087–1099.
periodontal disease Flichy-Fernández AJ, Ata-Ali J, Alegre-Domingo T, et al. The effect of orally administered probiotic Lactobacillus reuteri-containing tablets in peri-implant mucositis: a double-blind randomized controlled trial. J Periodontal Res. 2015;50(6):775–785.
bacterial vaginosis Martínez-Peña MD, Castro-Escarpulli G, Aguilera-Arreola MG. Lactobacillus species isolated from vaginal secretions of healthy and bacterial vaginosis-intermediate Mexican women: a prospective study. BMC Infect Dis. 2013;13:189. doi:10.1186/1471-2334-13-189.
respiratory tract priming Percopo CM, Rice TA, Brenner TA, et al. Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection. Antiviral Res. 2015;121:109–119.
prevent damaging inflammation Zelaya H, Tada A, Vizoso-Pinto MG, et al. Nasal priming with immunobiotic Lactobacillus rhamnosus modulates inflammation-coagulation interactions and reduces influenza virus-associated pulmonary damage. Inflamm Res. 2015;64(8):589–602.
ultraviolet radiation Satoh T, Murata M, Iwabuchi N, et al. Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice. Benef Microbes. 2015;6(4):497–504.
after UV exposure Ra J, Lee DE, Kim SH, et al. Effect of oral administration of Lactobacillus plantarum HY7714 on epidermal hydration in ultraviolet B-irradiated hairless mice. J Microbiol Biotechnol. 2014;24(12):1736–1743.
from drying out Nodake Y, Matsumoto S, Miura R, et al. Pilot study on novel skin care method by augmentation with Staphylococcus epidermidis, an autologous skin microbe—a blinded randomized clinical trial. J Dermatol Sci. 2015;79(2):119-126.
Leuconostoc mesenteroides Beganović J, Pavunc AL, Gjuračić K, et al. Improved sauerkraut production with probiotic strain Lactobacillus plantarum L4 and Leuconostoc mesenteroides LMG 7954. J Food Sci. 2011;76(2):M124–129.
bacteria as well Jung JY, Lee SH, Kim JM, et al. Metagenomic analysis of kimchi, a traditional Korean fermented food. Appl Environ Microbiol. 2011;77(7):2264–2274.
attributed to its consumption Vīna I, Semjonovs P, Linde R, Denina I. Current evidence on physiological activity and expected health effects of kombucha fermented beverage. J Med Food. 2014;17(2):179–188. doi:10.1089/jmf.2013.0031.
degradation of histamine Tsai Y-H. Degradation of histamine by Lactobacillus plantarum D103 isolated from miso, a fermented soybean food. International Association for Food Protection. 2015 Annual Conference. Abstract #P2-215.
antioxidant properties Watanabe N, Fujimoto K, Aoki H. Antioxidant activities of the water-soluble fraction in tempeh-like fermented soybean (GABA-tempeh). Int J Food Sci Nutr. 2007;58(8):577–587.
Saccharomyces cerevisiae Dlusskaya E, Jänsch A, Schwab C, Gänzle M. Microbial and chemical analysis of a kvass fermentation. Eur Food Res Technol. 2008;227(1):261–266.
also prevalent Osvik RD, Sperstad S, Breines E, et al. Bacterial diversity of aMasi, a South African fermented milk product, determined by clone library and denaturing gradient gel electrophoresis analysis. Afr J Microbiol Res. 2013;7(32):4146–4158. doi:10.5897/AJMR12.2317.
Cronobacter, Klebsiella Puerari C, Magalhães-Guedes KT, Schwan RF. Physicochemical and microbiological characterization of chicha, a rice-based fermented beverage produced by Umutina Brazilian Amerindians. Food Microbiol. 2015;46:210–217.
severity of colds Hughes C, Davoodi-Semiromi Y, Colee JC, et al. Galactooligosaccharide supplementation reduces stress-induced gastrointestinal dysfunction and days of cold or flu: a randomized, double-blind, controlled trial in healthy university students. Amer J Clin Nutr. 2011;93(6):1305–1311.
among the elderly Get active. Let’s move! letsmove.gov. http://www.letsmove.gov/get-active. Accessed August 9, 2015; Physical activity. Workplace Health Promotion. Centers for Disease Control and Prevention. http://www.cdc.gov/workplacehealthpromotion/implementation/topics/physical-activity.html. Accessed August 9, 2015; Belza B, PRC-HAN Physical Activity Conference Planning Workgroup. Moving ahead: strategies and tools to plan, conduct, and maintain effective community-based physical activity programs for older adults: a brief guide. Centers for Disease Control and Prevention. Atlanta, GA; 2007. http://www.cdc.gov/aging/pdf/community-based_physical_activity_programs_for_older_adults.pdf. Accessed August 9, 2015.
useful gut microbes Bermon S, Petriz B, Kajėnienė A, et al. The microbiota: an exercise immunology perspective. Exerc Immunol Rev. 2015;21:70–79.
independent of diet Kang SS, Jeraldo PR, Kurti A, et al. Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition. Mol Neurodegener. 2014;9:36. doi:10.1186/1750-1326-9-36.
high-fat diet Evans CC, LePard K, Kwak JW, et al. Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PLoS ONE. 2014;9(3):e92193. doi:10.1371/journal.pone.0092193.
more anti-inflammatory Allen JM, Berg Miller ME, Pence BD, et al. Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice. J Appl Physiol. 2015;118(8):1059–1066.
gut microbiome Choi JJ, Eum SY, Rampersaud E, et al. Exercise attenuates PCB-induced changes in the mouse gut microbiome. Environ Health Perspect. 2013;121(6):725–730.
“what good is it” Maurois A. Hopkins G, trans. The Life of Sir Alexander Fleming, Discoverer of Penicillin. New York, NY: E.P. Dutton & Co.; 1959; Brown, K. Penicillin Man: Alexander Fleming and the Antibiotic Revolution. The History Press, Kindle version; 2013.
Resources for Probiotics
the latest developments FDA reconsiders IND requirement for food research. International Scientific Association for Probiotics and Prebiotics. ISAPP Annual Meeting. http://www.isapp.net/Home. Accessed August 10, 2015.
prebiotics on their website FDA reconsiders IND requirement for food research. International Scientific Association for Probiotics and Prebiotics. ISAPP Annual Meeting. http://www.isapp.net/Probiotics-and-Prebiotics/Resources. Accessed August 10, 2015.
educational organization Probiotics for GI Health in 2012: issues and updates. Primary Issues. 2012. http://www.isapp.net/Portals/0/docs/News/merenstein%20sanders%20CME%20Probiotics.pdf. Accessed August 10, 2015.
available in Canada Skokovic-Sunjic D. Clinical guide to probiotic supplements available in Canada (2015 edition). Indications, dosage forms, and clinical evidence to date. Alliance for Education on Probiotics. http://www.isapp.net/Portals/0/docs/clincial%20guide%20canada.pdf. Accessed August 10, 2015.
studies and reviews Varankovich NV, Nickerson MT, Korber DR. Probiotic-based strategies for therapeutic and prophylactic use against multiple gastrointestinal diseases. Front Microbiol. 2015;6:685. doi:10.3389/fmicb.2015.00685; Bubnov RV, Spivak MY, Lazarenko LM, et al. Probiotics and immunity: provisional role for personalized diets and disease prevention. EPMA J. 2015;6(1):14.
Akkermansia muciniphila Dao MC, Everard A, Aron-Wisnewsky J, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. June 22, 2015. pii: gutjnl-2014-308778.
Bifidobacterium animalis Centanni M, Turroni S, Rampelli S, et al. Bifidobacterium animalis ssp. lactis BI07 modulates the tumor necrosis factor alpha-dependent imbalances of the enterocyte-associated intestinal microbiota fraction. FEMS Microbiol Lett. 2014;357(2):157–163.
Bifidobacterium breve Izumi H, Minegishi M, Sato Y, et al. Bifidobacterium breve alters immune function and ameliorates DSS-induced inflammation in weanling rats. Pediatr Res. 2015;78(4):407–416.
Bifidobacterium infantis Zuo L, Yuan KT, Yu L, et al. Bifidobacterium infantis attenuates colitis by regulating T cell subset responses. World J Gastroenterol. 2014;20(48):18316–18329.
Bifidobacterium longum Elian SD, Souza EL, Vieira AT, et al. Bifidobacterium longum subsp. infantis BB-02 attenuates acute murine experimental model of inflammatory bowel disease. Benef Microbes. 2015;6(3):277–286.
Enterococcus durans Avram-Hananel L, Stock J, Parlesak A, et al. E durans strain M4-5 isolated from human colonic flora attenuates intestinal inflammation. Dis Colon Rectum. 2010;53(12):1676–1686.
Enterococcus faecalis Wang S, Hibberd ML, Pettersson S, Lee YK. Enterococcus faecalis from healthy infants modulates inflammation through MAPK signaling pathways. PLoS ONE. 2014;9(5):e97523. doi:10.1371/journal.pone.0097523.
Faecalibacterium prausnitzii Quévrain E, Maubert MA, Michon C, et al. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease. Gut. June 4, 2015. pii: gutjnl-2014-307649.
Lactobacillus acidophilus Inoue Y, Kambara T, Murata N, et al. Effects of oral administration of Lactobacillus acidophilus L-92 on the symptoms and serum cytokines of atopic dermatitis in Japanese adults: a double-blind, randomized, clinical trial. Int Arch Allergy Immunol. 2014;165(4):247–254.
Lactobacillus amylovorus Finamore A, Roselli M, Imbinto A, et al. Lactobacillus amylovorus inhibits the TLR4 inflammatory signaling triggered by enterotoxigenic Escherichia coli via modulation of the negative regulators and involvement of TLR2 in intestinal Caco-2 cells and pig explants. PLoS ONE. 2014;9(4):e94891. doi:10.1371/journal.pone.0094891.
Lactobacillus casei Alipour B, Homayouni-Rad A, Vaghef-Mehrabany E, et al. Effects of Lactobacillus casei supplementation on disease activity and inflammatory cytokines in rheumatoid arthritis patients: a randomized double-blind clinical trial. Int J Rheum Dis. 2014;17(5):519–527.
Lactobacillus fermentum Jin P, Chen Y, Lv L, et al. Lactobacillus fermentum ZYL0401 attenuates lipopolysaccharide-induced Hepatic TNF-α expression and liver injury via an IL-10- and PGE2-EP4-dependent mechanism. PLoS ONE. 2015;10(5):e0126520. doi:10.1371/journal.pone.0126520.
Lactobacillus gasseri Spaiser SJ, Culpepper T, Nieves C Jr, et al. Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 ingestion induces a less inflammatory cytokine profile and a potentially beneficial shift in gut microbiota in older adults: a randomized, double-blind, placebo-controlled, crossover study. J Am Coll Nutr. 2015;34(6):459–469; Miyoshi M, Ogawa A, Higurashi S, Kadooka Y. Anti-obesity effect of Lactobacillus gasseri SBT2055 accompanied by inhibition of pro-inflammatory gene expression in the visceral adipose tissue in diet-induced obese mice. Eur J Nutr. 2014;53(2):599–606.
Lactobacillus helveticus Luo J, Wang T, Liang S, et al. Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat. Sci China Life Sci. 2014;57(3):327–335.
Lactobacillus johnsonii Xin J, Zeng D, Wang H, et al. Preventing non-alcoholic fatty liver disease through Lactobacillus johnsonii BS15 by attenuating inflammation and mitochondrial injury and improving gut environment in obese mice. Appl Microbiol Biotechnol. 2014;98(15):6817–6829.
Lactobacillus kefiranofaciens Hong WS, Chen YP, Dai TY, et al. Effect of heat-inactivated kefir-isolated Lactobacillus kefiranofaciens M1 on preventing an allergic airway response in mice. J Agric Food Chem. 2011;59(16):9022–9031.
Lactobacillus paracasei Simeoli R, Mattace Raso G, Lama A, et al. Preventive and therapeutic effects of Lactobacillus paracasei B21060-based synbiotic treatment on gut inflammation and barrier integrity in colitic mice. J Nutr. 2015;145(6):1202–1210.
Lactobacillus plantarum Hulst M, Gross G, Liu Y, et al. Oral administration of Lactobacillus plantarum 299v modulates gene expression in the ileum of pigs: prediction of crosstalk between intestinal immune cells and sub-mucosal adipocytes. Genes Nutr. 2015;10(3):461.
respiratory tract priming Percopo CM, Rice TA, Brenner TA, et al. Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection. Antiviral Res. 2015;121:109–119.
Lactobacillus reuteri İnce G, Gürsoy H, İpçi ŞD. Clinical and biochemical evaluation of lozenges containing Lactobacillus reuteri as an adjunct to non-surgical periodontal therapy in chronic periodontitis. J Periodontol. 2015;86(6):746–754.
Lactobacillus rhamnosus Cosenza L, Nocerino R, Di Scala C, et al. Bugs for atopy: the Lactobacillus rhamnosus GG strategy for food allergy prevention and treatment in children. Benef Microbes. 2015;6(2):225–232.
Pediococcus pentosaceus Kawahara M, Nemoto M, Nakata T, et al. Anti-inflammatory properties of fermented soy milk with Lactococcus lactis subsp. lactis S-SU2 in murine macrophage RAW264.7 cells and DSS-induced IBD model mice. Int Immunopharmacol. 2015;26(2):295–303.
Saccharomyces boulardii Everard A, Matamoros S, Geurts L, et al. Saccharomyces boulardii administration changes gut microbiota and reduces hepatic steatosis, low-grade inflammation, and fat mass in obese and type 2 diabetic db/db mice. MBio. 2014;5(3):e01011–14. doi:10.1128/mBio.01011-14.
VSL#3 blend Salim SY, Young PY, Lukowski CM, et al. VSL#3 probiotics provide protection against acute intestinal ischaemia/reperfusion injury. Benef Microbes. 2013;4(4):357–365.
by the Mayo Clinic Mayo Clinic Staff. Mediterranean diet: a heart-healthy eating plan. Healthy lifestyle: nutrition and healthy eating. Mayo Clinic. http://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/mediterranean-diet/art-20047801. Accessed August 10, 2015.
Treatment of Abdominal Obesity Watson RR, Zuckerman M, Zuckerman E. Nutrition in the Prevention and Treatment of Abdominal Obesity. San Diego, CA: Academic Press; 2014.
The Elimination Diet Segersten A, Malterre T. The Elimination Diet. New York, NY: Grand Central Life & Style; 2015.
Modern Health Crisis Prescott S. Origins: Early-Life Solutions to the Modern Health Crisis. Perth, Australia: UWA Publishing; 2015.
neurological systems Healthy child guide. The Neurological Health Foundation (NHF). https://www.neurologicalhealth.org/. Accessed August 10, 2015.
microbial dysbiosis and Schulz MD, Atay C, Heringer J, et al. High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity. Nature. 2014;514(7523):508–512.
microbiome and health Jeffery UB, O’Toole PW. Diet-microbiota interactions and their implications for healthy living. Nutrients. 2013;5(1):234–252. doi:10.3390/nu5010234.