Treating irritable bowel syndrome is challenging not only because the symptoms are so varied among patients but because new therapies are constantly being developed. Physicians a decade ago weren’t even talking about using probiotics or antibiotics to treat IBS symptoms. Once considered an “alternative” therapy, probiotics are now considered a standard treatment option for IBS by many health care providers. Researchers are actively studying probiotics and antibiotics to answer critical questions about the usefulness of these agents in treating IBS symptoms. Probiotics are sold at nearly all pharmacies and grocery stores, often with somewhat overstated claims about their benefits. Although probiotics and antibiotics have been briefly discussed in earlier chapters (see Chapters 17 and 19), so many patients have questions about these two classes of medications that in this chapter I will answer a list of frequently asked questions.
Probiotics are live organisms that, when ingested in adequate amounts, can affect the health of a person who has IBS. In other words, probiotics are supplements of living bacteria taken to alter, and presumably improve, the balance of native intestinal microflora (see below for a definition of microflora and gut flora). Although they are bacteria, they are classified as nonpathogenic (that is, not pathogens), meaning that they are not considered dangerous and will not cause an infection.
The gut flora (also called the gut microflora) are most accurately referred to as the gut microbiota. The gut microbiota is a large group of bacteria that normally resides within the gastrointestinal tract (primarily the large intestine). Estimates vary as to the precise number of different bacterial species within the gastrointestinal tract, but most authorities agree that there are approximately five hundred to one thousand different species of bacteria in the colon. Collectively, the number of live bacteria in the human colon is larger than the number of all other live cells combined throughout the rest of the body. The total number of bacteria that reside within the colon is staggering—over 1013 to 1014 cells—and weighs more than 4 pounds.
The gut microbiota have many different functions. These bacteria play a vital role in maintaining the health of the cells that line the colon. In addition, gut microbiota support the immune system of the gastrointestinal tract and aid in the processes of digestion and absorption of key nutrients.
Unfortunately, this is a question that remains unanswered. Different probiotics probably work differently, and although various people who have IBS may have similar symptoms, every person’s gut microflora are probably different from every other person’s. Many different theories have been proposed about why probiotics may improve symptoms in some people who have IBS. Researchers theorize that probiotics may
• add a previously deficient bacterial species
• restore the balance of “good” and “bad” bacteria
• improve gut immune function
• make the lining of the colon (referred to as the “barrier”) stronger and healthier
• improve the health of the cells that line the colon (the colonic epithelial cells)
In two separate randomized, placebo-controlled trials, the probiotic Lactobacillus plantarum 299V improved bowel habits and symptoms of abdominal pain in patients who had IBS in one of the studies but not the other. Two small studies of patients who had IBS and diarrhea showed that the probiotic VSL#3 appeared to improve symptoms of abdominal bloating and abdominal gas. By far the best studied probiotic for treatment of IBS symptoms is Bifidobacterium infantis. Two large, randomized, placebo-controlled studies in patients who had IBS (either with diarrhea predominance or alternating diarrhea and constipation) have shown that Bifidobacterium infantis 35624 improves symptoms of bloating, gas, and abdominal pain when compared to a placebo. Bifidobacterium infantis 35624 is currently sold under the trade name Align. More recently, the probiotic Bifidobacterium lactis DN-173-010A was tested in patients who have constipation-predominant IBS; it showed significant benefits for symptoms of bloating and constipation. More trials are needed to support this preliminary evidence for Bifidobacterium lactis with individuals who have IBS.
I generally recommend Bifidobacterium infantis (sold as Align) to my patients who have IBS and diarrhea symptoms and to those who have IBS and alternating symptoms of constipation and diarrhea. I tell people who have IBS and constipation that Align may help some symptoms of gas and bloating but that it probably won’t help their constipation symptoms (although Bifidobacterium lactis may). VSL#3 remains another option, although it is generally more expensive than Align, and there are fewer data to support its use at this time. Finally, because of the negative studies published to date, I do not recommend Lactobacillus to my patients.
Each new research study on the role of probiotics in the treatment of IBS raises more questions than answers. Just as no two people or medications are identical, no two probiotics are the same. Even for probiotics that seem very similar (because they are the same species of bacteria—Bifidobacteria), the different strains (the subtypes of bacteria within each major category) may have vastly different and even contrasting effects (for example, as noted above, Bifidobacteria infantis appears to act differently from Bifidobacteria lactis). Because all of the products are different from each other, it is impossible to make a sweeping statement that all probiotics must be used on a specific schedule for a certain time period. Rather, each probiotic must be evaluated individually. For example, some probiotics need to be used daily for 90 days to assess effectiveness, whereas others may need to be used twice daily for only 45 days.
The length of treatment will vary from probiotic to probiotic. Most research studies involving probiotics have lasted only 4 to 12 weeks. No studies have evaluated long-term safety and effectiveness (after 6 to 12 months of continuous use). Because options are limited, I generally recommend a 90-day trial of any probiotic to determine whether or not it is effective. If after 90 days no benefits are noted, then the probiotic should be stopped and a trial with another probiotic started. If a patient notices an improvement (whether an improvement in gas, bloating, or diarrhea) in IBS symptoms using a probiotic, then I generally recommend that the person continue the probiotic for at least six months. At that point, if symptoms are under control, then the probiotic can be stopped. However, many people note a slow return of symptoms after stopping the probiotic (regardless of type), and then they may begin taking them again.
Yes. No significant interactions with other medications have been identified.
Probiotics of many different forms (such as yogurt with live cultures) have been used for more than one hundred years by millions of individuals without any apparent side effects. Thus, on face value, probiotics appear quite safe. However, the probiotics contained in a capsule are somewhat different from probiotics that are in a natural food like yogurt. Only a few published research studies have addressed the safety of probiotics, and these only looked at a small number of probiotics.
Some concern about probiotics arose recently when patients who had severe acute pancreatitis may have become sicker or even died due to administration of probiotics. These patients were extremely ill to begin with, though, and they were administered large doses of probiotics through a tube directly into the small intestine. The apparent cause of death in some of these patients was decreased blood flow to the gastrointestinal tract (intestinal ischemia), not infection by a bacteria. There was no control group in this study, no patients were given a placebo, and only one dose was given. So, we don’t really know if these patients became sicker or died from the probiotic, because the study had only a small number of patients (which makes accurate statistical analysis difficult), because there was no control group, and because a larger dose than usual of probiotic was used. In addition, patients who have severe acute pancreatitis are completely different from patients who have IBS, so it is not helpful to apply the data from the pancreatitis group to a population who has IBS. Future trials will need to assess long-term safety of probiotics, but at present, they seem quite safe for nearly all populations (see below).
Due to concern about giving an immunosuppressed patient a live bacteria, I do not recommend using probiotics for patients who have a known immune deficiency, patients who have cancer or are undergoing treatment for cancer, patients who have a short gastrointestinal tract (this is called short gut syndrome), and newborn infants. Although I may be overly cautious, the theoretical risks of probiotics to these people, even if very low, outweigh the potential benefits of probiotics.
Yes. Probiotics are readily available from a multitude of sources. A word of caution: a probiotic is defined as a live organism that, when ingested, promotes improved health. Many probiotics now available on the market fail to meet that definition because they do not contain live organisms. Because probiotics are not regulated like food or medications, there is no guarantee that they will be shipped or stored under the appropriate conditions to guarantee that they remain healthy or even alive until you ingest them. One small study found that nearly 50 percent of probiotics purchased off the shelf were already dead. In addition, some probiotics have been found to be contaminated with other bacteria. Thus, you have the potential to ingest a bacteria that could make you sick or not help you at all.
As mentioned above, few probiotics have been tested in humans using scientific protocol. Some probiotics that were tested yielded negative results (meaning that they did not improve symptoms). But since probiotics are not under strict control like medications, they can still be sold even if they are not effective. Only one probiotic has been conclusively shown to survive passage through the gastrointestinal tract to reach the colon: Bifidobacterium infantis (sold as Align). So, it’s possible that a probiotic, even if alive and used in adequate amounts, might not survive passage into the large intestine and thus may not provide any benefits. As you contemplate using a probiotic, read the label carefully to determine what quality control measures are in place to guarantee safe arrival of the bacteria, and discuss your choice with your health care provider.
The Food and Drug Administration (FDA) is responsible for ensuring the safety of over-the-counter and prescription medications. Although regulation is a daunting task, the rules and regulations enforced by the FDA are part of the reason why medications available in the United States are generally safe. However, probiotics are not considered medications, and as such, they are not regulated by the FDA. Probiotics are considered foods (like yogurt and kefir) or dietary supplements. They do not have to undergo the rigorous testing involving thousands of patients that is required for traditional medications used to treat IBS symptoms (such as lubiprostone, alosetron, or linaclotide). In addition, unlike over-the-counter and prescription medications, which are advertised and sold only for certain conditions based on clinical studies and scientific evidence, manufacturers of probiotics can make any claim they want because they are not regulated. For these reasons, I recommend only a select few probiotics, those that have been researched using clinical studies involving people who have IBS.
A prebiotic is a substance that provides nutrients to a probiotic. Prebiotics are typically foods such as whole grains, complex carbohydrates, or fiber. Many patients and physicians believe that probiotics work better if a prebiotic is consumed just before taking the probiotic, but scientific evidence to support this is lacking.
Many individuals who have IBS are asking their doctors whether a stool transplant might help with their symptoms. As discussed earlier, the natural bacteria in the large intestine play a role in generating symptoms for many people who have IBS. However, these bacteria also ferment foods. When fermentation occurs, gas is produced, and this can cause the colon to stretch (distend), leading to intestinal cramps, spasms, bloating, pain, and urgent diarrhea. Since fecal flora seem to play such a critical role in symptom development, it is reasonable to wonder whether they could all be replaced with a different type of bacteria or with healthier bacteria.
The technical name for a stool transplant is fecal microbiota transplantation (FMT), and it is considered a probiotic technique. First described in 1958, it has recently received a lot of attention in the lay press. To perform a stool transplant, a fresh stool sample is taken from a healthy donor (a healthy first-degree relative is best), mixed with saline, processed and filtered and then infused into the patient during a colonoscopy. The theory is that “transplanting” or replacing a sick person’s normal microbiota with healthy bacteria will improve the patient’s intestinal symptoms. Casting aside the “yuck” factor, this therapy has been used to successfully treat severe Clostridium difficile (C. diff) infections that were resistant to standard antibiotic therapy. More than 90 percent of patients who had a severe C. diff infection (one that had failed antibiotic therapy) and who were treated with FMT stated that they would undergo an FMT again if necessary. Although FMT in people with severe ulcerative colitis or Crohn’s disease has been much less well studied, very limited data show that FMT may improve symptoms for them, as well.
No studies have yet evaluated FMT for people who have IBS. Although this will probably be an area of research in the future, physician researchers are approaching this topic cautiously, for many reasons. One, stool transplantation has some small risks associated with the procedure (undergoing a colonoscopy). Two, we still have much to learn about the gut microbiota; it is possible that, in an attempt to improve the health of patients, we may expose them to other disorders. Since FMT involves transferring five hundred to one thousand different types of bacteria from one person to another, the theoretical risks involved are huge. Three, at present we can only culture 10 to 20 percent of stool bacteria. Thus we cannot currently effectively “screen” a healthy donor to see if they have a disease that could be transmitted to the patient. For example, some practitioners are concerned that an autoimmune disorder such as rheumatoid arthritis could be transmitted from a seemingly healthy donor to a patient. For these reasons, stool transplantation is not yet a viable option for people who have IBS, but it may be in the future.
As with probiotics, no one really knows how antibiotics work to improve IBS symptoms. Currently, three main theories exist. One, some patients who have IBS have small intestinal bacterial overgrowth (SIBO; see Chapter 11). If a person has symptoms of gas, bloating, or diarrhea due to SIBO, then eliminating or reducing the offending bacteria from the small intestine with a course of prescription antibiotics makes sense. Two, some individuals may develop IBS symptoms because of an overabundance of bacteria in the large intestine. An antibiotic may be able to temporarily reduce (or suppress) the large number of bacteria, and this will normally improve symptoms of gas and bloating. Three, some people who have IBS may have an imbalance of certain bacteria in their colon (more “bad” bacteria than “good” bacteria), and an antibiotic could reduce or eliminate the problematic bacteria.
It is difficult to decide which antibiotic is best, because people who have IBS, even those with similar symptoms, have different intestinal micro-flora and will therefore respond to antibiotics differently. Current technology does not allow us to accurately measure or grow all of the different bacterial species in the colon. In fact, we can only accurately grow or culture 10 to 15 percent of the 500 to 1,000 species that reside within the human colon. Ideally, we could analyze a stool sample from a patient who has IBS and then recommend a specific antibiotic based on that analysis. Although that scenario may be possible in the future, currently it is not. Given these research deficiencies, I generally recommend one of two antibiotics for individuals who have IBS. Both of these antibiotics are considered nonabsorbable, meaning that very little of the medication (less than 1 percent) is absorbed from the gastrointestinal tract. Nonabsorbable antibiotics stay in the GI tract and generally do not cause any side effects outside the GI tract. The two antibiotics I currently recommend are rifaximin (also called Xifaxan) and neomycin. Keep in mind that, at the time this book was written, neither of these antibiotics, nor any other type of antibiotic, had been approved by the FDA for the treatment of IBS.
If you and your health care provider decide to use an antibiotic to try to improve your IBS symptoms, then I suggest trying either neomycin or rifaximin. Neomycin has been around for decades and is considered safe. In addition, since it is available as a generic prescription medication, it is usually fairly inexpensive. I generally recommend using 500 mg of neomycin 3 times daily for 10 days. Some physicians prescribe a higher dose (1,000 mg) for a longer period (up to 14 days), although there are no scientific studies comparing one regimen or time course to the other. One potential concern with neomycin is that patients may develop resistance to the medication, meaning that they may respond well to it initially but then not respond as well when it is prescribed again. For this reason, health care providers who choose to use an antibiotic use rifaximin first.
Used in Europe for more than 30 years, prescription rifaximin is currently approved by the FDA for the treatment of “traveler’s diarrhea” (for that disorder, it is considered safe and effective). Rifaximin has been tested in five large studies of people who have IBS. Two of the randomized, placebo-controlled studies involved a total of 1,258 patients. The results of these studies showed that rifaximin was much better than a placebo at treating IBS symptoms of gas, bloating, pain, and diarrhea. Although patients in these studies only took rifaximin for 14 days, many of them noted an improvement in their symptoms for 8 to 10 weeks after finishing the 2-week course of medication. As mentioned above, although not currently approved for the treatment of IBS, rifaximin can be taken 3 times daily at 550 mg for 14 days.
If you and your health care provider decide to use neomycin, I generally recommend just one course of this prescription antibiotic (500 mg taken 3 times daily for 10 days). Many patients do not respond to a second course of neomycin, even if their original symptoms initially improved. Rifaximin appears to be different, however. Many patients originally treated with rifaximin (550 mg 3 times daily for 14 days) note a recurrence of their symptoms 8 to 12 weeks after finishing the original course of antibiotics. A second course of rifaximin at that point may once again improve IBS symptoms in most patients (more than 50 percent). A few patients have been treated three or even four times with an antibiotic such as rifaximin to improve their symptoms of gas, bloating, and distention. Results vary; some patients report improvement after each course of the antibiotic, while others note that their level of response is less with each course of antibiotics. At the time of this book’s publication, a large research study was under way to evaluate the safety and efficacy of repeated courses of rifaximin in people with non-constipation IBS.
No. Antibiotics have risks (see below) and should not be used interchangeably for the treatment of IBS. In addition, other than those involving neomycin or rifaximin, no good scientific studies have evaluated the safety or efficacy of antibiotics for the treatment of IBS. So, unless there is definitive proof of small intestinal bacterial overgrowth (SIBO) in a patient who has IBS, I don’t recommend the use of any other antibiotic for the treatment of IBS symptoms.
Both neomycin and rifaximin are safe to use with nearly all other medications. However, other antibiotics have potential drug or diet interactions. For example, taking metronidazole (Flagyl) with alcohol can cause flushing, nausea, and vomiting, and some antibiotics can interfere with oral contraceptive agents. Many antibiotics cause vaginal yeast infections in women because they change the normal balance of “good” bacteria in the vagina. Review these potential interactions carefully with your health care provider.
Patients who have a prior history of C. difficile colitis, those whose immune systems are suppressed, and those on multiple medications should be cautious about using any type of antibiotic, even the nonabsorbable antibiotics (neomycin and rifaximin) described above. Note that although physicians and patients are concerned about the use of antibiotics and the potential complication of C. difficile colitis (see below), no case of C. difficile colitis has occurred in any of the rifaximin IBS studies.
Absolutely. There are several reasons why antibiotics should not be taken unnecessarily. One, inappropriate antibiotic use may lead to the development of antibiotic resistance, which means that the next time you need a specific antibiotic, you may not respond to that antibiotic (this could be a life-threatening concern). Two, antibiotics can change the composition of intestinal microflora, therefore altering digestion, changing the absorption of nutrients, and creating symptoms of gas and bloating. Three, inappropriate use of antibiotics can cause antibiotic-associated diarrhea. This type of diarrhea is a temporary condition that develops due to a change in intestinal microflora. It usually resolves on its own without any treatment. Four, antibiotics can cause Clostridium difficile colitis (also called C. difficile colitis, or C. diff, for short). Clostridium difficile colitis develops when the virulent bacterium C. difficile, which is normally found in the colon but is suppressed by “good” bacteria, grows unrestrained. The growth of this bacterium causes severe diarrhea that is potentially life threatening and requires treatment with antibiotics. For these reasons and more, antibiotics should not be used indiscriminately or liberally dispensed for the treatment of IBS symptoms.