Response to Probiotics Highly Individualized and Often not Beneficial

By Will Boggs MD

NEW YORK (Reuters Health) - The response of the gut mucosal microbiome to probiotic treatment is highly variable between individuals, is not reflected in stool microbiomes and could delay normalization after antibiotic treatment, researchers report.

"These results were very surprising and in particular the fact that probiotics human responses are so person-specific, the fact that only in responsive individuals we see a measurable effect of probiotics on the host, and the fact that we can predict the state of responsiveness mean that we need to transform from the current empiric, and universal 'one size fits all' probiotic use to one that is tailored to the individual and to the clinical context," Dr. Eran Elinav from the Weitzman Institute of Science, in Rehovot, Israel, told Reuters Health by email.

Nearly 4 million adults in the U.S. consume prebiotic or probiotic supplements, and up to 60% of healthcare providers prescribed probiotics to their patients for a variety of reasons, according to Dr. Elinav and his team. Their efficacy remains highly debated, however.

Most studies of probiotics have relied on characterization of the stool microbiome, and none have investigated the probiotic effects on the gut mucosal microbiome functionality.

Dr. Elinav and colleagues investigated the impact of probiotics in 2 separate studies reported in Cell, online September 6.

In the first study, they used endoscopy and colonoscopy to investigate the effect of prolonged consumption of an 11-strain probiotic preparation versus placebo on the gut mucosal microbiome and its function in 15 human volunteers.

Initial studies of mice showed that their stool microbiome only partially correlated with their gut mucosal microbiome, suggesting limited applicability of stool in fully assessing mucosal colonization. Results were similar in humans.

Human-targeted probiotics resulted in only low-level mucosal colonization in mice, which was mediated by resistance exerted by indigenous murine gut microbiome.

In humans, probiotic consumption resulted in universal shedding in stool but with highly individualized lower gastrointestinal mucosal colonization patterns, with some individuals showing permissive responses and others showing resistance to colonization by the probiotics.

The probiotic also had person-specific differential effects on the gut microbiome function and the host gut transcriptome.

"Only those individuals that are 'responsive' to probiotic gut mucosal colonization feature a transient effect of probiotics on the indigenous gut microbiome and host gene expression profile in the gut," Dr. Elinav said. "In contrast, 'resistant' individuals just pass their probiotics from one end to the other without having these impacts on the human host. The level of probiotics in stool cannot differentiate between the responsive and non-responsive individuals. This means that the current practice, followed by millions of individuals who consume probiotics with the hope that they improve their health and prevent disease, needs to be modified to one which is centered on the individual."

"Indeed, we describe several features of the human participants, even before they were ever exposed to probiotics, that enabled us to tell who would be a 'responder' and who would be a 'non-responder,'" he said.

In the second study, they investigated the impact of probiotics on the gut mucosal microbiome after antibiotic treatment.

In humans, antibiotics reversed colonization resistance to probiotics and enabled incremental gut colonization by probiotics, mainly in the large intestine, which led to long-term probiotic fecal shedding suggestive of stable colonization and active proliferation.

As a result of this colonization, probiotics delayed the post-antibiotic reconstitution of the indigenous human fecal and gut microbiome. In contrast, autologous fecal microbiome transplantation (FMT) induced a rapid and nearly complete fecal and gut microbiome reconstitution.

In other experiments, probiotics-secreted molecules inhibited the growth of indigenous human microbiome in vitro.

"This again demonstrates that a person-specific live bacterial approach is far superior to empiric probiotics, which in this setting may even harm the healthy host and microbiome post-antibiotic reconstitution," Dr. Elinav said.

"Our studies demonstrate in a very direct way that probiotics effects in healthy conditions are personalized and transient at best, and if you take a probiotic that you buy at your local supermarket, you have no way of knowing whether it would pass from one end to the other or alternatively whether the probiotics would actually colonize your gut, where they may (or may not) induce health-related benefits," he said.

"After antibiotics exposure, we point to probiotic consumption as very significantly prolonging the state of post-antibiotic disturbance to the human gut and associated microbes," added Dr. Elinav. "The consequences of these persistent and worrying disturbances merit further human studies."

Dr. Veena Taneja from Mayo Clinic, in Rochester, Minnesota, who recently reviewed microbial modulation of the gut microbiome for treating autoimmune diseases, told Reuters Health by email, "The most interesting aspect is the observation that host factors can determine permissiveness vs. resistance to colonization. This explains why some genetic factors are associated with decreases in certain (microbial) species. Immunogenetic control of the microbiome may be more robust than thought previously."

"Certain gut-derived commensals absent in patients may provide a means to change the gut function," she said. "This may be helpful to diseases which have genetic predispositions."

Dr. Taneja, who was not involved in the studies, said she did not it surprising that "fecal microbiota is a limited indicator of the gut microbiome."

"The upper gut has many facultative anaerobes that function much more closely with the immune system," she said. "However, changes caused by the microbiota in upper gut, if reflected in the stool microbiome or metabolome, may have a utility in generating biomarkers for diseases."

SOURCE: https://bit.ly/2wZyDxh and https://bit.ly/2Ny2JS5

Cell 2018.

(c) Copyright Thomson Reuters 2018. Click For Restrictions - https://agency.reuters.com/en/copyright.html

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