Akkermansia muciniphila modulates intestinal mucus composition to counteract high-fat diet-induced obesity in mice

Objective: This study investigates whether live Akkermansia muciniphila MucT supplementation can counteract obesity and metabolic dysfunctions induced by a high-fat diet (HFD) by modulating intestinal mucus production, secretion and composition. Design: C57BL/6J mice were fed an HFD with or without live A. muciniphila MucT (2×108 CFU per day) supplementation or a control diet for 6 weeks. Body weight, fat mass gain and metabolic markers were measured. Intestinal mucus characteristics were assessed via gene expression analysis of mucins and analysed mucin glycosylation by tandem mass spectrometry (MS/MS). Results: Mice receiving live A. muciniphila MucT exhibited reduced body weight gain and fat mass accumulation compared to HFD controls, without changes in muscle mass. A. muciniphila improved gut barrier integrity by increasing antimicrobial peptide expression in the jejunum and in the colon of HFD-fed mice. Furthermore, live A. muciniphila MucT influenced markers of goblet cell differentiation and restored the expression of mucin markers altered by HFD. Specifically, live A. muciniphila MucT counteracted HFD-induced mucin 3 (Muc3) expression depletion in the colon. Although the overall mucus thickness was not affected by live A. muciniphila MucT, the bacteria significantly modulated mucin glycans composition. Live A. muciniphila MucT did not change the gut microbiota composition. Conclusion: These findings highlight the protective effects of live A. muciniphila MucT against diet-induced metabolic dysfunctions by modulating adiposity, gut barrier integrity, mucus layer composition, and glycan profiles. This reinforces its potential as a therapeutic strategy for metabolic disorders associated with gut microbiota alterations.