Back-to-Back Studies on Probiotics Set Off Alarm Bells

Two new studies warn against taking a one-size-fits-all approach to probiotics.

Posted Sep 08, 2018

Probiotics are in the hot seat. Contrary to popular belief, there is a growing body of evidence that probiotics may not be as universally effective as once thought. In fact, new research suggests that in some cases consuming commercial probiotics may have negative consequences. 

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Source: CLIPAREA l Custom media

Here’s a quick timeline of the latest probiotic research that is setting off alarm bells for scientists around the globe: On June 19, a study was published linking probiotic use to brain fogginess and extreme belly bloating in some people. Another study, published on August 31, reported that consuming probiotics after taking antibiotics was linked to more severe intestinal infections in mice exposed to Cryptosporidium.  (For more see, "In a Brain Fog? Probiotics Could Be the Culprit" and "Unexpected Findings Cause Scientists to Rethink Probiotics.") 

Most recently, two back-to-back papers were published simultaneously on September 6 in the journal Cell showing that many people can’t successfully colonize standard probiotic microbiome in their gut. The scientists also found that consuming generic probiotic strains after taking antibiotics often delayed gut bacteria and gene expression from returning to their natural "naïve" state.

The latest two-part research on probiotics was spearheaded by researchers at the Elinav Lab of Immunology at the Weizmann Institute of Science in Israel and colleagues at the Tel Aviv Medical Center. Eran Elinav served as a senior author for both studies along with Eran Segal and his lab of computational biologists who focus on health and disease related to microbiome, nutrition, genetics, and gene regulation. 

"People have thrown a lot of support to probiotics, even though the literature underlying our understanding of them is very controversial; we wanted to determine whether probiotics such as the ones you buy in the supermarket do colonize the gastrointestinal tract like they're supposed to, and then whether these probiotics are having any impact on the human host," Eran Elinav said in a statement. "Surprisingly, we saw that many healthy volunteers were actually resistant in that the probiotics couldn't colonize their GI tracts. This suggests that probiotics should not be universally given as a 'one-size-fits-all' supplement. Instead, they could be tailored to the needs of each individual."

In the first Elinav study, “Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features,” the researchers recruited 25 human volunteers who underwent upper endoscopies and colonoscopies to obtain a baseline of gut microbiome in each person. 

Then, study participants were divided into one group that consumed a standard probiotic strain available in commercial supplements and a control group that was given a placebo. After two months of treatment, the researchers found that some people were so-called “resisters” who expelled the gut microbiomes in probiotics; others were identified as “persisters” who successfully colonized the generic probiotic strains in their GI tracts.

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Source: decade3d - anatomy online

Notably, after someone was tagged a “persister” or “resister” clear patterns emerged on how probiotics would impact his or her indigenous microbiome and gut bacteria profile. "Although all of our probiotic-consuming volunteers showed probiotics in their stool, only some of them showed them in their gut, which is where they need to be," Eran Segal said in a statement. "If some people resist and only some people permit them, the benefits of the standard probiotics we all take can't be as universal as we once thought. These results highlight the role of the gut microbiome in driving very specific clinical differences between people."

The second Elinav study, “Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT” involved a mouse model and human patients. One cohort of mice and a parallel human group was given the same probiotic strain used in the first study to see if they had more success repopulating their gut microbiota after a round of antibiotics. Another “watch-and-wait” cohort didn’t take probiotics to assist gut microbiome recovery after antibiotic-related depletion. A third cohort was given an “autologous fecal microbiome transplant” (aFMT) which consisted of a patient’s own gut microbiota that had been collected before he or she started a cycle of antibiotics.

Those who took probiotics did replenish gut microbiome more successfully than the “watch-and-wait” group. That said, there was also an unexpected backlash to probiotic use. The researchers were alarmingly surprised to discover that successful microbiome colonization via probiotics actually prevented the host's pre-antibiotic microbiome and gut gene expression profile from returning to its natural state for months after the treatment. But there is good news: Using aFMT resulted in the third group's native gut microbiome and gene expression profiles returning to normal within days after they stopped taking antibiotics.

There are four significant takeaways from this study: (1) murine gut mucosal probiotic colonization is only mildly enhanced by antibiotics, (2) Human gut mucosal probiotic colonization is significantly enhanced by antibiotics, (3) After taking antibiotics, probiotics delay gut microbiome and transcriptome reconstitution in mice and humans, (4) Autologous fecal microbiome transplant (aFMT) restores mucosal microbiome and gut transcriptome reconstitution. 

"Contrary to the current dogma that probiotics are harmless and benefit everyone, these results reveal a new potential adverse side effect of probiotic use with antibiotics that might even bring long-term consequences," Elinav said in a statement. "In contrast, replenishing the gut with one's own microbes is a personalized mother-nature-designed treatment that led to a full reversal of the antibiotics' effects." Segal added, "This opens the door to diagnostics that would take us from an empiric universal consumption of probiotics, which appears useless in many cases, to one that is tailored to the individual and can be prescribed to different individuals based on their baseline features."

References

Niv Zmora, Gili Zilberman-Schapira, Jotham Suez, Uria Mor, Mally Dori-Bachash, Stavros Bashiardes, Eran Kotler, Maya Zur, Dana Regev-Lehavi, Rotem Ben-Zeev Brik, Sara Federici, Yotam Cohen, Raquel Linevsky, Daphna Rothschild, Andreas E. Moor, Shani Ben-Moshe, Alon Harmelin, Shalev Itzkovitz, Nitsan Maharshak, Oren Shibolet, Hagit Shapiro, Meirav Pevsner-Fischer, Itai Sharon, Zamir Halpern, Eran Segal, Eran Elinav. "Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features." Cell (First published: September 6, 2018) DOI: 10.1016/j.cell.2018.08.041

Jotham Suez, Niv Zmora, Gili Zilberman-Schapira, Uria Mor, Mally Dori-Bachash, Stavros Bashiardes, Maya Zur, Dana Regev-Lehavi, Rotem Ben-Zeev Brik, Sara Federici, Max Horn, Yotam Cohen, Andreas E. Moor, David Zeevi, Tal Korem, Eran Kotler, Alon Harmelin, Shalev Itzkovitz, Nitsan Maharshak, Oren Shibolet, Meirav Pevsner-Fischer, Hagit Shapiro, Itai Sharon, Zamir Halpern, Eran Segal, Eran Elinav. "Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT." Cell (First published: September 6, 2018)  DOI: 10.1016/j.cell.2018.08.047

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