Nov. 20, 2015
Now is a great time to learn more about the supporting data and incorporate first-generation probiotics into your practice when appropriate.
The microbiome is among the hottest topics in medical and scientific research. The National Institutes of Health and private foundations have invested hundreds of millions of dollars in research to define and characterize the human microbiome. In the next decade, billions more will be devoted to deciphering how microbes influence human health in a positive manner. The implications of this field now go well beyond GI tract diseases to include disorders ranging from autism and allergies to obesity. It is indeed an exciting time for those of us in the practice of gastroenterology who should be looked to as leaders in this revolutionary new field. Alas, as with most of science, it takes an extensive amount of time for the translation of preclinical research findings to reach clinical practice. Thus, it is not surprising that of the myriad high-profile discoveries made utilizing sophisticated microbial sequencing technology, none have led to any changes in patient care to date.
In fact, most of the human studies on probiotics that guide our clinical practice today were influenced by the pioneering theories of Elie Metchnikoff from over a century ago. He was the Russian zoologist who first postulated that host-friendly bacteria, such as those found in yogurt, could enhance human health. As a testament to his influence, most human clinical trials and data for probiotics on human health to date have been conducted using milkfermenting bacteria such as Lactobacillus and Bifidobacteria species. Although this background may seem inauspicious, a substantial body of work supports the benefits of these “firstgeneration” probiotics. Multiple Lactobacillus and Bifidobacteria species positively influence host physiology through a variety of mechanisms. These include, but are not limited to, competing with gut pathogens, exerting anti-microbial effects, enhancing gut barrier function, modulating motility and sensation, impacting host immune function and contributing to important metabolic functions such as short chain fatty acid production and even drug metabolism. With all these ascribed benefits, it is no wonder that we’ve seen at least some positive human clinical trials using these present day probiotics. So, where does the data currently support the use of probiotics in clinical practice? The following bullet points summarize the topic:1
- Antibiotic-associated diarrhea: Several Lactobacillus strains as well as the probiotic yeast Saccharomyces boulardii are capable of limiting the duration or intensity of diarrhea associated with taking common antibiotics such as cephalosporins and macrolides. Individuals might consider taking their probiotic supplement at a different time than the antibiotic to enhance the likelihood of probioticsurvival and efficacy. I frequently recommend a reputable Lactobacillus-containing probiotic (such as Culturelle) to patients who have experienced this in the past. I also found this strategy to be effective for my own children.
- Infectious gastroenteritis: Bacterial and viral infections can be bothersome not only during the acute phase, but can also lead to bowel irregularity for weeks afterward. Taking a Lactobacillus probiotic or S. boulardii may shorten the duration of both the acute illness and extended symptoms.
- Irritable bowel syndrome: IBS symptomatology is complex, but several studies suggest certain probiotic products reduce symptoms in some individuals. Align, a specific Bifidobacteria strain, improved global IBS scores more than a placebo or a Lactobacillus probiotic in one study. In my own practice, I find Align to be helpful for some patients, particularly with bloating and associated dysphoria. The multi-strain probiotic VSL#3 is another option and meta-analysis suggests that Bifidobacteria are more effective than Lactobacillus strains.2
- Inflammatory bowel disease: A variety of probiotic preparations have been studied using varied clinical endpoints for IBD.3 In short, probiotics have not been found to be beneficial in Crohn’s disease. In ulcerative colitis and pouchitis, multi-strain probiotics such as VSL#3 may be effective as an addon or single agent for some patients with mild or even moderate disease activity. In my own clinical practice, I have found only a few instances of sustained objective success for this strategy.
- Hepatic encephalopathy: Recent intriguing data suggests that single or multi-strain probiotics may improve signs of hepatic encephalopathy and its complications including hospitalization.4 Confirmative studies will be needed to move this strategy into clinical practice.
Probiotics have a place in managing GI symptoms and conditions
While I believe that probiotics have a place in managing GI symptoms and conditions, please consider a few caveats and basic principles when recommending probiotics to your patients:
- Probiotic supplement efficacy is typically moderate as compared to traditional pharmaceuticals. As such, they are often better as a supplement to, rather than replacement for, traditional pharmaceuticals.
- Probiotic strain(s), quantity and preparation make a difference. Multi-strain or even dual-strain probiotics are not necessarily better. For example, several singlestrain probiotics effectively reduce antibiotic-associated diarrhea. However, a large prospective randomized clinical trial recently failed to show antibiotic-associated diarrhea reduction when using a multi-strain Lactobacillus and Bifidobacteria probiotic product.5
- Quality control remains an important issue. My colleague makes this very clear and his remarks certainly apply to a great number of supermarket shelf products. This fact underscores the importance of learning the data and basing your recommendations on reliable brands that have been proven in human clinical trials.1
- Probiotics are generally considered to be safe in most patients. This includes IBD patients on TNFα inhibitors. However, urge more severely immunocompromised patients to avoid probiotics and make sure patients with indwelling catheters do not break open the capsules.
A few final things to consider. First, patients (friends and family members too) may ask you if they should routinely take a probiotic or consume a probiotic yogurt for their “general digestive health.” These questions are likely prompted by product labels indicating that their probiotic “improves digestive health” or “strengthens the immune system.” These statements are specifically vague as FDA has not approved any health claims for probiotics. I usually respond by encouraging the individual to monitor if his or her own symptom response goals are being met by taking the probiotic for a month. If not, their money is probably better spent elsewhere.
Microbiota-gut-brain interactions are an active area of research that will hopefully lead to new clinical strategies for mood disorders. The specifics of how this strategy might be best employed are still being investigated, but consider this: probiotic studies often find that patients taking the probiotic “felt better” in some way than those taking placebo. This “feeling better” frequently occurred even in the absence of an objective improvement in GI-disorder-related symptoms. For example, my colleague’s group recently reported that celiac disease patients taking probiotics had a higher celiac disease related quality of life, even though they experience higher disease symptom scores.6 So, keep in mind that taking probiotics could actually impact your patient’s diseaserelated quality of life, even without objectively changing their disease symptoms.
I will close by briefly mentioning socalled “next-generation” probiotics. While I personally remain optimistic for the translation of these new non-Lactobacillus or Bifidobacteria probiotics or perhaps probioticderived products, many questions remain to be answered. What will their safety profile be? Will they be effective in pill form? Will individual probiotic species be the answer or will novel consortium-based probiotic products be tailored to treat specific diseases as is nearing reality for Clostridium difficile?7 With these questions still looming and patient interest in “first-generation” probiotics at an all-time high, now is a great time to learn more about the supporting data and incorporate them into your practice when appropriate.
Dr. Ciorba has lectured on behalf of AbbVie, UCB and Takeda. He is currently a member of the Crohn’s and Colitis Foundation of America Research Panel.
1. Ciorba MA. A gastroenterologist’s guide to probiotics. Clin Gastroenterol Hepatol 2012;10:960-8.
2. Ford AC, Quigley EM, Lacy BE, et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol 2014;109:1547-61; quiz 1546, 1562
3.Shen J, Zuo ZX, Mao AP. Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn’s disease, and pouchitis: meta-analysis of randomized controlled trials. Inflamm Bowel Dis 2014;20:21-35.
4.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;147:1327-37 e3.
5. Allen SJ, Wareham K, Wang D, et al. Lactobacilli and Bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2013;382:1249-57.
6. Nazareth S, Lebwohl B, Tennyson CA, et al. Dietary Supplement Use in Patients With Celiac Disease in the United States. J Clin Gastroenterol 2015;49:577-81.
7.DS P, Kelly C, Khanna S, et al. Ser-109, An Oral, Microbiome-based Therapeutic, Is Efficacious For The Treatment Of Recurrent C. Difficile And Eliminates Enterobacteriacea And Vancomycin-resistant Enterococci Colonizing The Gut ICAAC Meeting 2014 2014.