Every day, millions of people take probiotics – preparations that contain living bacteria to boost their immune system, prevent disease or repair the negative effects of antibiotics. However, the benefits of probiotics have never been medically proven.

Researchers from the Israeli Weizmann Institute of Science now suggest evidence from mouse and human experiments that the most commonly used probiotics are less than beneficial.

According to two back-to-back reports released on September 6 in the journal cellIt is not even clear whether probiotic bacteria really populate the digestive tract or, if they do, how they affect the microbiome of indigenous intestinal bacteria.

For the first study, 25 volunteers underwent upper endoscopy and colonoscopy to examine their microbiome composition and function in different colon regions. Fifteen of these volunteers were then divided into two groups: one received a probiotic 11 strain preparation and the second received placebo pills.

Artwork from "Personalized Good Mucosal Colonization Resistance to Empiric Probiotics is Associated with Unique Host and Microbiome Features," Cell, September 6, 2018.

Three weeks after the four-week treatment, all participants underwent a second upper endoscopy and colonoscopy to assess their response to the probiotics or placebo, and were then observed for another two months.

The researchers discovered that intestinal colonization of probiotics is very individual. In general, there were "persisters" whose guts harbored the probiotic microbes and "resisters" who drove them away.

The scientists found that they could predict whether a person would be a persistence or a resistance by merely examining the profile of the microbiome and the gene expression profile for the initial profile. Persisters showed changes in their native microbiome and gut gene expression profile, while resisters did not show such changes.

The double-track study was led by researchers in the laboratories of Prof. Eran Elinav of the Immunology Department and Prof. Eran Segal of the Department of Computer Science and Applied Mathematics, in collaboration with Prof. Zamir Halpern, Head of Gastroenterology in Tel Aviv Sourasky Medical Center.

"Our findings suggest that probiotics should not be given to the general public as a nutritional supplement" for any size, "Elinav said. "Instead, they could be tailored to each individual and their specific needs, and our findings even suggest how such personalization could be done."

Segal said the findings support earlier dietary studies that revealed a similar individual response to food and "highlighted the role of the gut microbiota in driving very specific clinical differences between people."

Probiotics for antibiotics can not work

In the second study, researchers tested the wisdom of commonly given advice for people to take probiotics against the effects of antibiotics.

They investigated whether probiotics colonize the intestine after antibiotic therapy and how this affects the human host and its microbiome.

Researchers administered broad spectrum antibiotics to 21 volunteers, who then had to undergo upper endoscopy and colonoscopy to observe changes in the gut and its microbiome after antibiotic treatment.

Next, the volunteers were randomly assigned to one of three groups. The first was a watch and wait group that recovered its own microbiome. The second group was administered the probiotic 11 strain cocktail over a period of four weeks. The third group was treated with an autologous fecal microbiome graft (aFMT) consisting of their own bacteria, which were collected before they had the antibiotic.

The scientists discovered that the antibiotic had paved the way for the probiotics and they colonized the human gut much easier than in the previous study.

To their surprise, this was not an advantage: probiotic colonization actually prevented the gene expression and microbiome from returning to normal pre-antibiotic configurations for months.

In patients treated with aFMT, the native gut microbial recolonization and gut gene expression profiles returned to normal within a few days.

Graphic of "Post-Antibiotic Good Mucosal Microbiome Reconstitution is Impaired by Probiotics and Enhanced by Autologous FMT," Cell, September 6, 2018.

"These results," said Elinav, "show a new and potentially alarming adverse side-effect of probiotic use with antibiotics, which could even lead to long-term consequences, in contrast to personalized treatment – filling the gut with one's own microbes a complete reversal of the effect of the drugs. "

Because probiotics are among the most widely traded, over-the-counter supplements in the world, these results can have immediate, far-reaching effects.

"Contrary to the current dogma that probiotics are harmless and benefit everyone," Segal said, "we suggest that probiotics should be tailored to individuals, or that such treatments as autologous FMT may be indicated in some cases. "

Dr. Niv Zmora, Jotham Suez, Gili Zilberman-Schapira and Uria Mor from Elinav's lab conducted the two projects in collaboration with other members of the Elinav and Segal Laboratories as well as Weizmann and Tel Aviv Sourasky scientists and clinicians Hai Academic College and the MIGAL Institute in Galilee. Segal is head of the Weizmann Institute's crown human genome center.

The cell Reports can be viewed here and here.


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