To use—or not use—probiotics: Safety information is grossly lacking

Reporting of adverse events (AEs) or harms resulting from probiotics, prebiotics, and synbiotics is not adequate. Therefore, decisions regarding the safety of these interventions cannot yet be made, according to a recent systemic review of clinical trials published in the Annals of Internal Medicine.

In light of this dearth of information, clinicians should exercise caution in discussing and recommending these types of supplements to patients.

Prebiotics consist of foods that act as food for human microflora and are given to improve or balance microflora within the body. Examples of prebiotics, which are usually high-fiber foods, include whole grains, bananas, onions, garlic, and soybeans. Probiotics are foods or supplements comprised of live microorganisms that maintain and/or improve normal microflora in the body. Examples of probiotic foods include yogurt, kimchi, kombucha, and sauerkraut. Finally, synbiotics are food ingredients or dietary supplements that contain both prebiotics and probiotics.

According to the National Center for Complementary and Integrative Health, almost 4 million adults in the United States use probiotics or prebiotics for a wide variety of conditions, including weight loss, gastrointestinal conditions, asthma, infections, eczema, and depression.

Yet most research on prebiotics and probiotics has failed to provide any specific data on the possible harms of these supplements.

In a recent analysis, researchers led by Aïda Bafeta, PhD, Université Paris Descartes-Sorbonne Paris Cité, France, searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science and assessed the safety of probiotic use by identifying 384 randomized, controlled trials in which researchers investigated probiotics, prebiotics, and synbiotics.

In a full 28% of these trials, no harms-related data were shown, and no safety results were published in 37%.

Even more compelling was that 80% did not include the incidence of serious adverse events (SAEs), and 98% included no definitions for either AEs or SAEs, patient withdrawals due to AEs, or the number of AEs or SAEs per study group.

MDLinx got some hands-on advice for clinicians about probiotics from Geoffrey Preidis, MD, PhD, member of the American Gastroenterological Association Center for Gut Microbiome Research & Education scientific advisory board. Dr. Preidis commented on this current review from Bafeta et al., and offered some recommendations on safe probiotic use.

MDLinx: What is the role of pre/probiotics in treating digestive conditions?

Dr. Preidis: Clinical trials using probiotics have illustrated a variety of beneficial effects for individuals with various digestive conditions, as well as for newborns in the neonatal intensive care unit. Among the most studied conditions are antibiotic-associated diarrhea, inflammatory bowel disease, irritable bowel syndrome, and acute gastroenteritis. 

Despite a growing volume of research, defining a precise role for probiotics remains challenging. Although some trials report clear beneficial effects, the majority of studies provide insufficient evidence to determine whether probiotics were beneficial. Furthermore, different trials often test different probiotic species, strains, dosing regimens, and durations of therapy.

Some studies use live bacteria in yogurt, while other studies use dried microbes in capsule form. The trials often are designed very differently, use different methods to measure outcomes, and enroll very different patient populations.

All of these variables make it difficult to compare results from one study to another. Nonetheless, there is enough promising overall evidence to suggest that one day, we might be able to define a role for probiotics in treating specific digestive conditions.

In contrast, there is currently much less clinical data to support the use of prebiotics for digestive conditions, but this is likely to change more research is completed. Clearly, we have not yet realized the full potential of prebiotics and probiotics. 

MDLinx: Is the use of these supplements becoming more common? If yes, why?

Dr. Preidis: Yes. The National Center for Health Statistics reported that use of probiotics or prebiotics increased four-fold between 2007 and 2012. Although reasons for this trend were not specifically addressed, among the factors that could be responsible are growing public awareness of the importance of beneficial microbes to human health, promising results from recent laboratory studies, and aggressive marketing by stakeholders within this multi-billion dollar industry.

MDLinx: Do clinicians typically ask patients about their use of these supplements? Should they?

Dr. Preidis: To date, only a few studies have examined clinicians' practice patterns regarding probiotic and prebiotic supplements. Most likely, the frequency with which clinicians ask patients about their use of microbiome-targeting supplements varies widely from provider to provider.  

Given everything we are learning about the important role gut microbes play in health and disease, clinicians should be asking their patients regularly about their use of probiotics, prebiotics, and other supplements.

MDLinx: Are there patients in whom they would be contraindicated?

Dr. Preidis: Although we generally regard probiotics and prebiotics to be safe for most healthy people, some patients with serious underlying medical conditions, including those with a weakened immune system due to chemotherapy or organ transplantation or other critical illness, could have a greater risk of serious adverse events.

It is important to speak to one's doctor about potential risks and benefits prior to starting any new microbiome-targeting supplement.

MDLinx: What sorts of safety issues are possible with these supplements?

Dr. Preidis: In healthy individuals, if side effects are present, typically they are limited to mild digestive symptoms such as gas—a common byproduct of dietary fiber fermentation by gut microbes. In rare circumstances, patients—most of whom were critically ill—have developed infections in the bloodstream or in other places outside of the gastrointestinal tract after taking probiotics.

Microbiome-altering agents could adversely affect metabolism over the short- or long-term. In theory, probiotics could over-activate the immune system or transfer antibiotic-resistance genes to other gut bacteria. These theoretical concerns have not been identified in humans to date.

Finally, adverse events including allergic reactions could be caused by other ingredients in the supplement. These possibilities highlight the importance of knowing exactly what each supplement contains, and discussing potential risks and benefits with one's doctor.

MDLinx: Can you comment on the importance of the review conducted by Bafeta et al.?

Dr. Preidis: This is an important study that explores the level of detail reported in clinical trials of probiotics, prebiotics, and synbiotics. The authors conclude that the majority of recently published studies lack sufficient details regarding safety and side effects. It's important to note that they did not find evidence suggesting that these products are unsafe; rather, they highlight the need to report safety data more rigorously in the future.

Although we still generally consider probiotics, prebiotics, and synbiotics to be safe for most people, these findings reiterate the importance of speaking to one's doctor before starting a new microbiome-targeting therapy.

The American Gastroenterological Association (AGA) has reviewed available data regarding the use of probiotics for digestive conditions and developed guidance for gastroenterologists and patients. Information that can help patients talk to their doctor about the role of probiotics in treating their gastrointestinal symptoms can be found on the AGA website here.