Commensal microbiota in the gastrointestinal tract contribute to the regulation of host metabolic health. In addition, complex metabolic diseases are associated with imbalances in microbiome composition. For instance, obesity and type 2 diabetes mellitus are correlated with decreased abundance of the commensal bacterium Akkermansia muciniphila. A new clinical study by Patrice Cani and co-workers now explores the feasibility, safety and tolerability of administering A. muciniphila to humans to reduce the risk factors that characterize the metabolic syndrome.

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Prior to this study, translational research in rodents by Cani’s group and others had indicated that increasing A. muciniphila abundance might be a promising therapeutic strategy to enhance metabolic health. “We found that the bacteria were reinforcing the gut barrier leading to the blockage of gut permeability,” explains Cani. “This improved glucose tolerance and enhanced the efficiency of using fat and glucose in metabolic tissues.”

The researchers have now undertaken a randomized, double-blind, placebo-controlled pilot study in 32 volunteers with obesity and insulin resistance. The study participants were administered either live or pasteurized A. muciniphila, or placebo, daily for 3 months.

complex metabolic diseases are associated with imbalances in microbiome composition

The primary end points of the study were safety, tolerability and readouts of metabolic health. Secondary outcomes were intestinal barrier function and gut microbiota composition. The researchers found that, following the 3-month regimen, study participants who were given the bacteria had improved insulin sensitivity, reduced plasma levels of total cholesterol and decreased plasma levels of biomarkers for liver dysfunction and inflammation compared with the placebo group. In addition, body weight and fat mass were slightly reduced in the groups that received A. muciniphila supplementation.

The intervention was safe, well tolerated and did not affect the overall gut microbiome structure. “Furthermore, the tests in humans confirm what had already been observed in mice; the pasteurized form of A. muciniphila was more efficient than the live bacteria on several parameters,” adds Cani. “The most important thing is to confirm the results of this small pilot study in a larger cohort.”

This article is modified from the original in Nat. Rev. Endocrinol. (https://doi.org/10.1038/s41574-019-0241-3).