A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice

• Published in: Nature medicine Vol. 23; no. 1; pp. 107 - 113
• Main Authors: Plovier, Hubert, Everard, Amandine, Druart, Céline, Depommier, Clara, Van Hul, Matthias, Geurts, Lucie, Chilloux, Julien, Ottman, Noora, Duparc, Thibaut, Lichtenstein, Laeticia, Myridakis, Antonis, Delzenne, Nathalie M, Klievink, Judith, Bhattacharjee, Arnab, van der Ark, Kees C H, Aalvink, Steven, Martinez, Laurent O, Dumas, Marc-Emmanuel, Maiter, Dominique, Loumaye, Audrey, Hermans, Michel P, Thissen, Jean-Paul, Belzer, Clara, de Vos, Willem M, Cani, Patrice D
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2017; Nature Publishing Group
• Subjects: 631/326/41/2533; 692/699/2743/2037; Adipose Tissue - drug effects; Adult; Akkermansia muciniphila; Animals; Bacteria; Biomedicine; Blood Glucose - drug effects; Blood Glucose - metabolism; Blotting, Western; Body fat; Cancer Research; Care and treatment; Chromatography, Liquid; Development and progression; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Digestive system; Digestive tract; Disease Models, Animal; Dyslipidemia; Dyslipidemias - metabolism; Energy absorption; Female; Genetic aspects; Gram-negative bacteria; Health aspects; Humans; Immune system; Infectious Diseases; Insulin; Insulin Resistance; Intestinal microflora; Intestine; Intestines - drug effects; Intestines - metabolism; Laboratorium voor Microbiologie; letter; Male; Membrane proteins; Membrane Proteins - pharmacology; Metabolic Diseases; Metabolic Syndrome - metabolism; Metabolism; Metabolomics; Mice; Mice, Obese; Microbiological Laboratory; Microbiologie; Microbiology; Microbiota; Middle Aged; Molecular Medicine; Neurosciences; Obesity; Obesity - metabolism; Pasteurization; Proteins; Toll-Like Receptor 2 - drug effects; Toll-Like Receptor 2 - metabolism; Toll-like receptors; Verrucomicrobia; VLAG; WIMEK
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.4236

Akkermansia muciniphila , a member of the gut microbiome, has been shown to improve metabolism in mice. Here it is reported that its pasteurization further improves this effect, and that one of its membrane proteins by itself has a similar benefit. Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition 1 , 2 , 3 , 4 , 5 , 6 , 7 . We previously demonstrated that administration of Akkermansia muciniphila to mice prevents the development of obesity and associated complications 8 . However, the underlying mechanisms of this protective effect remain unclear. Moreover, the sensitivity of A. muciniphila to oxygen and the presence of animal-derived compounds in its growth medium currently limit the development of translational approaches for human medicine 9 . We have addressed these issues here by showing that A. muciniphila retains its efficacy when grown on a synthetic medium compatible with human administration. Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidemia in mice. These improvements were notably associated with a modulation of the host urinary metabolomics profile and intestinal energy absorption. We demonstrated that Amuc_1100, a specific protein isolated from the outer membrane of A. muciniphila , interacts with Toll-like receptor 2, is stable at temperatures used for pasteurization, improves the gut barrier and partly recapitulates the beneficial effects of the bacterium. Finally, we showed that administration of live or pasteurized A. muciniphila grown on the synthetic medium is safe in humans. These findings provide support for the use of different preparations of A. muciniphila as therapeutic options to target human obesity and associated disorders.