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.