Diet-dependent gut microbiota remodeling by pasteurized Akkermansia muciniphila, specialized pro-resolving mediators, and B vitamins in mice

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BACKGROUND: A high-fat diet induces alterations in gut microbiota composition, which can be partially or completely restored through targeted dietary interventions. The present study investigated the effects of pasteurised Akkermansia muciniphila, Specialized Pro-resolving Mediators (SPMs), and B vitamins on host metabolism and gut microbiota composition in C57BL/6J mice under standard (SD) or high-fat (HFD) conditions. METHODS: Morphometric parameters, such as body weight, waist circumference, BMI, epididymal fat mass, and metabolic parameters, such as total cholesterol, HDL, LDL, VLDL, triglycerides, TG/HDL-C ratio, and glycemia, were determined. Gut microbiota composition was characterized by 16SrRNA gene sequencing, and microbial alpha-diversity was assessed using Shannon and Simpson indices. Differences in amplicon sequence variants (ASVs) were analysed. RESULTS: All interventions attenuated key features of HFD-induced metabolic dysfunction, particularly adiposity and lipid dysregulation, whereas improvements in glucose homeostasis remained limited, indicating mitigation of the metabolic phenotype. HFD induced a robust remodeling of the gut microbiota, including an increased Firmicutes:Bacteroidota ratio, enrichment of Lachnospiraceae, and depletion of SCFA-producing taxa and fiber-degrading bacteria, without consistent effects on alpha-diversity. Under SD, A. muciniphila exerted extensive changes, associated with taxa previously linked to SCFA production, but, under HFD, its effects were attenuated and constrained by dietary conditions. SPMs and B vitamins induced selective changes in bacterial groups associated with carbohydrate metabolism and microbial cross-feeding networks. Under HFD, no significant effects of SPMs were detected; in the contrast, B vitamins promoted changes in bacterial groups involved in complex carbohydrate degradation and fermentation processes. CONCLUSIONS: Together, these findings support a model in which the three interventions, whose effects are shaped by dietary context, act as modulators rather than reshapers of microbial communities. Importantly, they appear to influence the gut microbiota through distinct and non-overlapping mechanisms, rather than inducing uniform patterns of microbial modulation.

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