Akkermansia muciniphila modulates intestinal mucus composition to counteract High-Fat Diet-induced obesity in mice
Gut Microbes
Objective: This study investigates whether Akkermansia muciniphila supplementation can counteract obesity and metabolic dysfunctions induced by a high-fat diet (HFD) by modulating intestinal mucus production, secretion and composition.
Methods: C57BL/6J mice were fed an HFD with or without live Akkermansia muciniphila (2×108 CFU per day) supplementation 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 A. muciniphila 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. Furthermore, A. muciniphila influenced goblet cell differentiation by normalizing the expression of key transcription factors, including kruppel-like factor 4 (Klf4) and hes family bHLH transcription factor 1 (Hes1), and restored the expression of mucin markers altered by HFD. Specifically, A. muciniphila counteracted HFD-induced mucin 2 (Muc2) depletion in the caecum and increased mucin 3 (Muc3) expression in the colon. Additionally, A. muciniphila significantly modulated mucin glycosylation, reducing HFD-induced increases in sialylated glycans while restoring glycan prevalence to control levels.
Conclusion: These findings highlight the protective effects of A. muciniphila 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.
Gut Microbes
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