Once you understand how your microbiome works, you can gain a sense of mastery over the entire co-partnership. That is where really effective self-care emerges. As I learned from my own personal path with NCDs and my microbiome, this can be really self-empowering.
Your microbiome is your co-partner and there are some deep secrets and behavioral quirks that you need to know about it. Since you are going through life together, it could be time to set some rules and boundaries when it comes to the shared living space that is your body. I don’t know if your body is your temple, but I do know it is the house where your microbiome lives. It’s time to appoint yourself head of the homeowners association (HOA) for your body. Your microbiome can’t go off throwing wild teenage parties and trashing the house while your attention is elsewhere, dealing with life’s stresses. To ensure helpful behavior, you need to train your microbiome just like you would train your kids or your pets, all the while becoming its caretaker and protector and enjoying life together. Training your microbiome is a little like becoming an effective parent or an effective dog trainer. You need to have a good handle on the trainee. You need to understand certain unhealthy tendencies and behaviors, recognize when they arise, and have a plan to minimize any damage and turn those behaviors into something productive. Earlier in the book, I emphasized your mighty majority microbes. But for self-care, now is the time for your minority mammalian self to take charge. You can and should be respectful of your microbes but, nevertheless, be fully in charge of your own body even if the microbes outnumber you. You want to understand microbe behavior much like Cesar Millan understands dog behavior. There are horse whisperers and dog whisperers—and there will be microbiome whisperers.
Sometimes microbes operate not just independently but as a pack, and they can easily shift into a pack mentality. Quite often that is not a good thing for your body. That is where you lose control just the same as if your pet dog were enticed to join a neighborhood pack of dogs intent on bringing down a deer. But just as Cesar Millan knows dogs, your knowing about your microbiome’s pack tendency allows you to become a master trainer of your microbiome. To really get the upper hand, bringing the microbial part of you in line with your health goals, it is useful first to think like a microbe and then to set some goals. What does the social life of your microbes look like? How do they live, socialize, and protect themselves? What kind of microbes do you really want to cohabit with?
Different people from different geographic areas with long experiences with different diets have different lead bacteria in their guts. They have different enterotypes. It is clear that people from different ethnic groups, geographic regions, and even lifestyles will host different populations in their microbiomes. This is not shocking since the microbiome, or second genome, is a product of ancestry and environment (the latter also including dietary patterns). For this reason, what constitutes an ideal, normal gut microbiome in Kunming, China, is not necessarily identical to one you would find in healthy adults in Boulder, Colorado; Maracaibo, Venezuela; or Adelaide, Australia. Different ethnic makeup, different environments, and different diets result in overlapping yet different profiles for the microbiome.
When you consider working on your gut microbiome, you are likely to find that some changes are easy to make and sustain while others just don’t seem to take hold. Researchers believe that is the difference of working within your predominant pattern of gut microbes (i.e., your own enterotype) versus working across enterotypes. You may not know your enterotype at the moment, but there are lots of companies offering microbiome analysis services that can tell you. You don’t have to know your enterotype to change your microbiome. It is simply something to be aware of as you pursue self-care.
However, there is a second useful measure of microbiome health, and that is its richness or diversity. It is not enough to get your lead gut bacteria in line with your diet and ancestry. You need to ensure that your microbiome has the diversity needed and the right microbial players in place to perform all the necessary co-partner functions for your body. This goes right to the core of the rare microbe in your gut performing a critical function being the microbe you most want to nurture and protect. That is, in effect, knowing your weakest link. There are plenty of the most prevalent bacteria in your gut around, but always having enough of the really rare, functionally important bacteria can be the difference between health and disease. In training your microbiome, these two concepts, knowing your lead bacteria and keeping your microbiome diverse, need to coexist.
Evidence suggests that microbial diversity is generally beneficial and should be one of our training targets. In other words, it is helpful for us to have enough different species and strains of bacteria and archaea to provide all the metabolic pathways, neuroactive chemicals, and immune signals that our body needs to be in balance and to function well. If we are not sufficiently diverse in our microbiome, that is usually a warning sign of an impending or existing health problem. There are two important pieces of evidence. First, many different categories of diseases (e.g., allergic, autoimmune, inflammatory, metabolic) are associated with microbiome profiles in which bacterial species are missing or the numbers of key bacteria are too few to perform vital tasks. Although high diversity of microbes does not always guarantee good health, it is often a health risk to have a restricted diversity of microbial species compared with healthy controls.
Second, an international team of researchers recently analyzed the fecal, oral, and skin bacterial microbiomes of a remote group of Yanomami Amerindian village people living in the Alto Orinoco region of the state of Amazonas in Venezuela. These people had no known prior contact with people of European descent. These indigenous people of the Amazon jungle spanning Venezuela and Brazil had the highest diversity of bacteria ever found in a group of humans. Genetic analyses also suggested that they had a broader array of genes at their disposal for biological functions. Are the indigenous people disease-free? Certainly not. They die, but it is usually of infectious diseases. While some of the infectious-disease mortality is due to local pathogens, a significant portion of it is also caused by newly encountered pathogens introduced via contact with outsiders. You might say their mortality profiles look like a European population of many centuries ago.
What they don’t have is important. It is our current global epidemic of NCDs. In fact, hypertension and obesity were nonexistent among the Yanomami sampled in recent decades. However, a 2014 study compared obesity rates among jungle Yanomami with those now living in two villages with a westernized lifestyle (called transculturation). As had been seen in earlier studies, there was no obesity among jungle adult Yanomami. In contrast, there were high rates of obesity (44 percent and 89 percent) in adults from two different villages with different degrees of nutritional transitions to a westernized lifestyle. The take-home message is that there are lifestyles where the NCD epidemic does not exist, and those seem to feature the combination of a nonwesternized diet supporting a more diverse microbiome. The goal will be to identify the changes that get us back closer to living in nature while still reaping the benefits of civilization’s progress. There is some middle ground where the NCD epidemic is defeated.
Probiotics have been suggested as tools to shift our physiology from a pro-tumor-growth state to an anti-tumor environment, particularly when it comes to gastrointestinal cancers. In a human study demonstrating that probiotics can shift the gut microbiomes of colon cancer patients, researchers in Shanghai, China, showed that tissue from cancer patients had restricted microbial diversity compared with healthy controls. Additionally, the cancerous tissue was dominated by bacteria from the genus Fusobacterium. Because heavier loads of these specific bacteria in this type of cancer are associated with poor immune response against the tumor and shorter patient survival, it has been suggested that Fusobacterium load is a helpful indicator of patient prognosis. Taking a probiotic both reduced the presence of Fusobacterium and increased the density and diversity of gut microbes overall. Determining whether probiotics can actually extend the life of colorectal cancer patients will take more study. However, these results suggest that a mix of microbes that seem to promote tumor growth and prevent immune attack can be changed using probiotics.
Drawing upon the human garden analogy, you will be training your microbiome garden, in general, to be prolific in terms of numbers of each vegetable and more diverse in terms of types of different vegetables (microbes).
Also, pay attention to your soil and climate type as you work on the microbial garden (that would mean playing to your enterotype as you work toward a healthier balance of microbes). Shifting within the enterotype may be easier than shifting between enterotypes just because they have been engrained in your ancestry for a very long time. The good news is that healthy microbiomes exist within all major enterotypes examined to date.
A good example illustrating why it may help to work within an enterotype comes from a recent analysis of gut microbiota from 303 school-age children living in rural and urban areas from five different countries in Asia. The microbial profiles of the children fell into two major enterotypes, those dominated by Prevotella bacteria (P-type bacteria) or those dominated by Bifidobacterium or Bacteroides bacteria (B-type bacteria). Subtypes were found within the two major enterotypes. A majority of the children in China, Japan, and Taiwan had the B-type lead bacteria enterotype, while a majority of children in Indonesia and the Khon Kaen region in Thailand had the P-type lead bacteria enterotype. Notably, each major enterotype included children who had a healthy body mass index as well as those who were obese. So in training your microbiome, you can move from an unhealthy state to a healthier state yet stay within the same major enterotype (lead bacteria group).
Beyond the lead bacteria there were other country-of-origin and rural-versus-urban differences. For example, a bacterium known as Dialister invisus was detected from 67 percent of children in Japan but only 18 percent of children from cities in other countries. Some differences were found that might relate to the type of rice that was eaten and its resistant starch content (which varies between the rice in Japan and Indonesian rice). Also, the research found a distinct rural-versus-urban difference in the predominant gut microbiome of children within Thailand. Most children in rural Thailand had the P-type profile while most children in Bangkok had the B-type profile. But in a separate study of Bangkok residents focusing on vegetarians, their gut microbiome looked more like that of people from rural areas of the country (who also ate more vegetables than their counterparts in Bangkok). This study contributes to the idea that cities in general are not that beneficial for our microbiome except among the few who go out of the way to lead healthier lifestyles (such as creating a personal farm-type lifestyle in the city).
In a recent study, two different groups of healthy children in geographically distinct areas of Thailand were analyzed for their gut microbe composition. In the northeast part of the country people eat different meats, a wide variety of carb types (including fermented rice), and a diversity of fruits and vegetables. In contrast, in the central region of Thailand people eat more rice, breakfast cereals, and cow’s milk in their diets. Distinct differences in the microbiomes were associated with these different region-based diets. One of the differences between children was higher representations of Lactobacillus and Bacteroides fragilis in the northeast. It is important to keep in mind that the span of these dietary differences would involve not just the children in the samples but their parents as well.
Other comparisons of the gut microbes among children on two continents and in four different regions showed that the region can be as or more important than the continent in affecting the features of the microbiome. In this instance, the exact cause (i.e., diet, latitude, other factors) of the regional differences is not known.
It is not just gut microbes that are affected by geography, climate, and diet. A climate and geography comparison was made of the microbes found in saliva among adults from Alaska, Germany, and Africa. The result was that Alaskans and Germans were more similar to each other than either area was to the Africans. However, there were core groups of microbes that were always seen together regardless of the sample locations.
All this research shows that, ultimately, the goal should be to match specific dietary adjustments and rebiosis strategies with your enterotype whenever possible. Have them meet you where you are now. Don’t try to find some perfect magic elixir that works for everyone on earth. You would be working against centuries of superorganism programming. Find the mix that works for you personally. If it is time for more personalized medicine, it is also time for more personalized self-care. Make any self-care recommendation prove itself by the results in your body. You will feel them.
We can use the group behavioral tendencies of microbes to our benefit. Like people, and cows and fish and insects, microbes communicate with one another and can act both individually and as groups. This communication goes on both inside and outside of your body. You want your microbes associating with the right crowd and not engaging in any gang-like behavior that would damage you. One of the processes through which the microbes communicate and act in union is called quorum sensing. The name literally refers to the fact that our microbes can detect when other microbes are around, as well as the types and numbers of those other microbes. They can then decide if they will participate in group microbe projects. Some of the projects may be in your best interest, some projects not. That is where you as a properly prepared trainer of the microbiome need to step in.
Quorum sensing is a process of communication among bacteria and archaea that influences group behavior. It allows microbes to detect the density of populations in a given environment—your body, for instance—and to detect and signal other environmental changes. Because they are in constant communication about the surrounding conditions, they can coordinate responses that simulate that of a whole intact organism. Among the changes that bacteria undergo is to alter their metabolism based on the available nutrients, avoid the accumulation of toxic chemicals, and protect themselves against other microbes. Pathogens will use quorum sensing to defend against the human immune response and to increase their capacity to infect rapidly (often called virulence factors). There are literally chemical circuits that can become activated at the same time in thousands of microbes that promote group changes and action. Different types of bacteria (e.g., gram-positive versus gram-negative bacteria) utilize different forms of quorum sensing systems.
In one type of quorum sensing strategy, proteins called autoinducers are produced by the bacteria, aiding communication with other microbes. It is a process that can result in changes made as a herd. In some cases these changes can be beneficial for human health and in other cases can present a greater chance of disease. By understanding how and when quorum sensing works, it is possible to manipulate those signals to help maintain a healthy microbiome and reduce the risk of dysbiosis-induced disease.
One of the examples where a pathogen uses quorum sensing to increase virulence is found in the skin bacteria Staphylococcus aureus. Normally, the bacteria results in only minor skin infections if the skin barrier is broken, allowing its entry. However, under different circumstances, it can lead to serious, life-threatening infections. S. aureus is a major cause of infection within hospitals. This bacterium can turn pathogenic when different combinations of the quorum sensing genes are activated and the virulence of S. aureus increases significantly.
Comparisons have been made among Lactobacillus species, where certain species are rigid in their physiological responses and others can seemingly adapt to different niches. In a study from the Netherlands investigators discovered that the Lactobacillus species L. plantarum, which is found not only in the human gut but also in fermented foods and plants, contains more quorum sensing genes and related components than do other Lactobacillus species with highly restricted niches (e.g., L. johnsonii).
The quorum sensing molecule produced by bacteria may be recognized by human mammalian receptors as well. At least one study suggests that the mammalian part of humans may be able to listen in to bacterial chatter transmitted by quorum sensing molecules. Much like keeping track of your tweens’ and teens’ activities on social media such as Twitter, Instagram, and Facebook, it is good to stay on top of quorum sensing chatter within your microbiome.
While quorum sensing is a natural strategy for cooperation among microbes, specific knowledge of the pathways involved in quorum sensing allows a new opportunity for microbiome management. There are three main ways in which quorum sensing can be used to improve health and reduce the risk of disease: (1) provide indicators of impending changes in our microbiome, (2) provide potential drug targets to block impending or ongoing infections, and (3) provide new opportunities to adjust the composition and status of the microbiome in different tissues.
In the first situation, quorum sensing signals can give us a measure indicating that potential harmful changes are under way in our microbiome. The signals are what are called biomarkers and could be used to help distinguish between harmful and healthful environmental exposures (e.g., potentially harmful exposures to environmental toxins or useful ingestion of certain probiotics) as well as determine the effectiveness of medical therapies. Depending on the microbes involved, certain environmental exposures could change quorum sensing in a way that would present us with an impending health risk.
One of these is a tendency of certain pathogens to gang together, change their own physiology, and form what are called biofilms. Biofilms are very difficult for us to attack immunologically or through the use of antibiotics. But there may be a solution to biofilms found in our increasing understanding of quorum sensing. For example, some of our gut bacteria have the capacity to block biofilm formation by gut pathogens. Among the products they produce is an antibiofilm enzyme called acylase. We can use our microbes’ own strategies to police destructive gangs among pathogens and control unruly microbes within us.
Measuring quorum sensing signals gives us a powerful tool. Changes in these signals could be an early warning signal that could help prevent disease. Other desired quorum sensing signals could help us to determine if a given probiotic is producing a desired outcome in the gut, skin, airways, or urogenital tract.
This is a real-world scenario. By using altered quorum sensing signals, it should be possible to interfere with the conversion of pathogenic bacteria into dangerous infective agents. If these bacteria can’t act as a group and bind tightly to epithelial cells lining our tissues, the bacteria can’t form biofilms to thwart immune attack. With such interference, pathogenic bacteria lose their tools and advantages for producing disease.
Here is an example of how gut bacteria can use quorum sensing to block a pathogen. In an intriguing study involving both Bangladeshi children and germ-free mice, investigators from three continents found that a specific commensal bacterium in the guts of normal healthy children in Bangladesh (Ruminococcus obeum) can use intermicrobial communication to reduce the ability of the cholera-causing bacterium Vibrio cholerae to colonize and cause disease in the human gut. The commensal bacteria produce a quorum sensing effect on the Vibrio cholerae that changes its gene expression and restricts its ability to become established in the gut and cause disease.
I suspect these types of natural and deliberately manipulated, microbiome-centered strategies will be used to reduce the risk of some infectious diseases in the future.
Not only humans, animals, and plants need to worry about attack from viruses. Bacteria and archaea inhabiting our body can be invaded by viruses as well. While we rely on our multicellular immune system to protect us from viral and pathogenic bacteria infections, our own microbes don’t have the luxury of lymphocytes and macrophages and all the many different kinds of immune cells that we have. Are they totally defenseless? It turns out they have a rather ingenious plan.
Bacteria and archaea have their own equivalent of an immune system, only they don’t have any army of specialized immune cells to recruit and send forward into the attack. Instead, they mobilize different types of enzymes to literally cut viruses to shreds. Where we use cells to attack our enemies, they use enzymes. Their system is called CRISPR.
CRISPR stands for clustered regularly interspaced short palindromic repeat, which is a type of immune system for prokaryotes (single-celled microorganisms without a nucleus, such as bacteria and archaea). Like the human immune system, CRISPRs can recall having seen an outside threat before. This is called immunological memory. With this memory the second exposure to the same challenge (such as infection with a virus) allows the immune response to be more specific against the pathogen, move faster, and utilize more resources. In this case, the bacteria want to be protected from viruses (known as bacteriophages) and other mobile pieces of DNA that could compromise the bacteria’s integrity and/or subvert their functions.
In some ways the bacterial CRISPRs’ attack on viruses looks a little like the metal-munching Sentinels mobilized against Zion in the Matrix movie trilogy. The enzymes rip through viral DNA, destroying viruses and helping the bacteria and archaea to maintain their integrity. But the story behind these bacterial enzymes is proving to be much more than it originally seemed.
If recently revealed secrets of the microbiome have already spawned a revolution both in safety evaluation and health care, then there is even more to be gleaned from our microbial partners. The striking discovery that bacteria have their own type of immune system has paved the way for new human and animal therapies as well as plant science technologies. Because bacteria are highly susceptible to attack by viruses, they need a way to protect their own integrity. For this purpose, they have developed a unique genetic-based strategy for protecting themselves from these attacks, as discovered by Jennifer Doudna at the University of California, Berkeley, and Emmanuelle Charpentier at the Helmholtz Centre for Infection Research and described by Carl Zimmer in Quanta Magazine.
This protection involves the bacterial capacity to capture pieces of DNA from an invading virus, store them in specific places within their own bacterial genome, convert the viral DNA copy into copies of RNA, and then mobilize the RNA pieces along with specific DNA-digesting enzymes to attack the DNA of the same invading virus. The RNA sequences exquisitely match the viral DNA such that the enzymes only destroy the DNA of interest. For the bacteria, this is a specific defense with little energy wasted and few adverse side effects.
The entire process relies on two series of gene sequences. The first are the already described CRISPRs. Next to these are genes for producing the DNA-cutting enzymes called Cas, which stands for CRISPR-associated genes. These enzymes troll the bacterium, carrying the RNA copy made from viral DNA as a landing pad. Once this landing pad latches onto the matching viral DNA, the enzyme goes to work cutting the DNA into pieces and destroying the viral genome. It is the Cas enzyme seeking a precise match for the RNA that brings specificity into the attack. CRISPR and Cas make an effective team. A particular Cas, Cas9, appears to be very important in giving the whole immune-like defense system its capacity of memory.
Notably, this bacterial immune defense is specific against the single invading virus and does not destroy other DNA. Because of this specificity and the fact that the bacteria use prior exposure to the virus to their own advantage, the bacterial defense represents a type of adaptive immune response. In fact, there appears to be a type of bacterial vaccination event that occurs when the viruses that invade bacteria (also called bacteriophages) have defective phages. Exposure of bacteria to these defective phages can lead to CRISPR sequences being set up but give the bacteria time to get ready for a real intact virus attack. Also, there is selection against what would be considered an autoimmune type of response (where the sequences and enzymes overlap with the host bacterial genome).
The CRISPR-Cas9 system of our bacteria and archaea has many overlaps with our own immune system. Besides the aspect of memory of prior attacks, bacteria are able to select against their own DNA and in favor of foreign DNA to place in the CRISPR area of the chromosome. The bacterial CRISPR-Cas9 system protects the bacteria’s genes from attacks by invading foreign genetic material. The system also overlaps with the way our own mammalian immune system interacts with the external environment, including our microbiome. The human immune system is known not only to protect against pathogenic invasion of the host but also to create a steady state interaction with the environment and proper function within tissues. In many ways the CRISPR-Cas9 system of bacteria mimics this physiological function as well. Researchers have found that CRISPR can be present even in the absence of viruses. The question is, what is it doing in those situations? One idea is that it allows bacteria to respond to environmental changes by changing their own cell envelope physiology.
CRISPR-Cas9 will have biotechnological applications well beyond the microbes and will affect future medicine and therapies. In effect, we are learning from our microbes how to better battle disease. But for now it is helpful that this gene-based strategy of our microbes allows them to function as if they had their own type of immune system, which can sample their environment, interact with it, and protect them from environmental attack.
These remarkable developments in our understanding of the technical details of microbe behavior are what enable us to personally take charge of the microbes within us. But another line of research has perhaps even more amazing implications for our daily sense of well-being. Let us turn to the effect of the microbiome on our psychology.