Microbial metabolite-mediated modulation of enteroendocrine and immune pathways by Lactiplantibacillus pentosus CECT 8039 in early diet-induced obesity.

INTRODUCTION: The gut microbiota-enteroendocrine axis contributes to the regulation of host energy homeostasis through microbial metabolites and satiety-related signaling. This study evaluated whether Lactiplantibacillus pentosus CECT 8039 (L. pentosus BB) modulates microbial fermentation, enteroendocrine responses, and metabolic and immune parameters associated with early diet-induced obesity. METHODS: A dynamic multi-compartment colonic fermentation model was used to assess changes in cultivable microbial groups and short-chain fatty acid (SCFA) concentrations following probiotic treatment. Fermentation samples were subsequently evaluated in STC-1 enteroendocrine cells and a Caco-2/THP-1 co-culture model. In parallel, the metabolic and immunomodulatory effects of L. pentosus BB were assessed in mice fed a high-fat diet (HFD) for 28 days. RESULTS: Probiotic treatment selectively modulated cultivable microbial groups, increasing lactic acid bacteria and decreasing Clostridium spp. across the three simulated colonic compartments, while other groups showed region-dependent changes. Acetate, propionate, and butyrate concentrations increased in all three compartments; in the ascending colon, they increased 2.53-, 7.34-, and 5.08-fold, respectively, relative to the end of stabilization. Fermentation samples collected after probiotic treatment increased GLP-1 release, reaching statistical significance in the transverse-colon condition, while Pyy mRNA expression increased significantly in the ascending and descending colon conditions and Cck expression increased significantly in all three compartments. In vivo, HFD-fed mice showed a 34.9 ± 5.5% body-weight gain, whereas probiotic supplementation was associated with a 13.2 ± 4.7% lower relative body-weight gain compared with the HFD control group. In HFD-fed mice, probiotic supplementation reduced circulating resistin by 25.8 ± 9.4% and leptin by 85.5 ± 20.1%, whereas the change in adiponectin was not statistically significant. Immune responses were heterogeneous and depended on the experimental context. DISCUSSION: L. pentosus BB was associated with increased colonic SCFA concentrations, enhanced enteroendocrine responses, and partial attenuation of HFD-associated metabolic alterations. These findings support a functional association between probiotic-modulated microbial fermentation and host endocrine and metabolic responses, although direct SCFA-mediated causality remains to be established.