Bifidobacterium breve B2798 Attenuates Diet-Induced Obesity Through Gut-Adipose Crosstalk

Obesity is driven by complex interactions between diet, gut microbiota, and host metabolism. Here, we investigate whether the probiotic Bifidobacterium breve B2798 mitigates high-fat diet (HFD)-induced metabolic dysfunction in C57BL/6J mice. Male mice received HFD for 12 weeks, followed by 12 weeks of B. breve B2798 or saline. Probiotic treatment significantly reduced body weight gain, epididymal and inguinal fat mass, and liver weight, and improved insulin sensitivity, without affecting glucose tolerance. Multi-omics integration revealed that B. breve B2798 partially reversed HFD-induced gut dysbiosis, notably decreasing Coriobacteriia and Deferribacteres while enriching Faecalibaculum rodentium . Fecal metabolomics showed elevated hydroxy fatty acids (e.g., 12-hydroxystearic acid) and modulation of lipid metabolism pathways. In epididymal adipose tissue, transcriptomics uncovered restored expression of Slc2a4 and Acsm3 , with gene set enrichment analysis highlighting enhanced fatty acid oxidation, thermogenesis, and oxidative phosphorylation. Integrated miRNA–mRNA analysis identified regulatory networks potentially mediating these effects. These findings demonstrate that B. breve B2798 ameliorates obesity-related metabolic disturbances via coordinated gut microbiota remodeling and adipose tissue reprogramming, supporting its potential as a microbiome-targeted therapeutic strategy.