Clostridium butyricum attenuates subcutaneous fat deposition by remodeling intestinal extracellular vesicle-mediated gut-adipose communication in pigs

Abstract Whether intestinal extracellular vesicles (EVs) mediate the regulatory effect of C. butyricum on subcutaneous fat deposition remains poorly understood. Here, we investigated the effect of dietary C. butyricum supplementation on subcutaneous adiposity in Jinhua pigs and explored the potential involvement of colonic EVs in gut-adipose communication. C. butyricum reduced backfat thickness and adipocyte size, accompanied by lower expression of lipogenic and adipogenic genes. Furthermore, C. butyricum improved gut barrier function, reduced inflammatory markers, and increased microbial short-chain fatty acid production. Metagenomic analysis showed that CB-enriched microbial genomes harbored expanded carbohydrate-active enzyme repertoires, suggesting enhanced carbohydrate utilization and fermentation capacity. Intestinal EV profiling revealed that C. butyricum altered the abundance and miRNA cargo, which miR-1285 emerging as a functional candidate linked to adipocyte lipid metabolism. Integrated correlation and target analyses linked CB-responsive EV miRNAs with microbial functional guilds, pathways related to the regulation of adipogenesis and lipogenesis. Functionally, colonic EVs from CB-treated pigs and a miR-1285 mimic reduced lipid accumulation in adipocytes and suppressed lipogenic gene expression. These findings suggest that intestinal EVs may serve as a regulatory signal connecting C. butyricum -driven gut microbial remodeling to adipose lipid metabolic reprogramming.