Microbial metabolite-mediated modulation of enteroendocrine and immune pathways by Lactiplantibacillus pentosus CECT 8039 in early diet-induced obesity.
Veciana-Galindo C, Núñez-Delegido E, et al. • Frontiers in endocrinology • 2026
Lactiplantibacillus pentosus CECT 8039 was associated with increased colonic SCFA concentrations, enhanced enteroendocrine responses, and partial attenuation of HFD-associated metabolic alterations, supporting a functional association between probiotic-modulated microbial fermentation and host endocrine and metabolic responses.
Key Findings
Results
Probiotic treatment selectively modulated cultivable microbial groups in a simulated colonic fermentation model, increasing lactic acid bacteria and decreasing Clostridium spp. across all three simulated colonic compartments.
A dynamic multi-compartment colonic fermentation model was used to assess changes in cultivable microbial groups.
Lactic acid bacteria increased across ascending, transverse, and descending colonic compartments.
Clostridium spp. decreased across all three compartments.
Other microbial groups showed region-dependent changes rather than consistent trends across compartments.
Results
Short-chain fatty acid (SCFA) concentrations of acetate, propionate, and butyrate increased in all three colonic compartments following probiotic treatment.
In the ascending colon, acetate increased 2.53-fold, propionate increased 7.34-fold, and butyrate increased 5.08-fold relative to the end of stabilization.
Increases were observed across ascending, transverse, and descending colonic compartments.
SCFAs were measured following Lactiplantibacillus pentosus CECT 8039 treatment in the fermentation model.
Results
Fermentation samples collected after probiotic treatment increased GLP-1 release in STC-1 enteroendocrine cells, reaching statistical significance in the transverse-colon condition.
GLP-1 release was evaluated in STC-1 enteroendocrine cells exposed to fermentation samples.
Statistical significance was reached for GLP-1 release under the transverse-colon fermentation condition.
The ascending and descending colon conditions showed increases that did not reach statistical significance for GLP-1.
Results
Pyy mRNA expression increased significantly in ascending and descending colon fermentation conditions, and Cck expression increased significantly in all three compartment conditions in STC-1 cells.
Pyy mRNA expression was significantly increased under ascending colon and descending colon fermentation conditions.
Cck expression increased significantly under all three fermentation compartment conditions (ascending, transverse, and descending colon).
These enteroendocrine gene expression results were obtained from STC-1 enteroendocrine cells treated with probiotic fermentation samples.
Results
In HFD-fed mice, probiotic supplementation was associated with a 13.2 ± 4.7% lower relative body-weight gain compared with the HFD control group over 28 days.
Mice were fed a high-fat diet (HFD) for 28 days.
HFD-fed mice showed a 34.9 ± 5.5% body-weight gain.
Probiotic-supplemented HFD mice showed 13.2 ± 4.7% lower relative body-weight gain compared with the HFD control group.
The probiotic used was Lactiplantibacillus pentosus CECT 8039 (L. pentosus BB).
Results
Probiotic supplementation reduced circulating resistin by 25.8 ± 9.4% and leptin by 85.5 ± 20.1% in HFD-fed mice, while the change in adiponectin was not statistically significant.
Circulating resistin was reduced by 25.8 ± 9.4% in probiotic-supplemented HFD mice compared to HFD controls.
Circulating leptin was reduced by 85.5 ± 20.1% in probiotic-supplemented HFD mice compared to HFD controls.
The change in adiponectin did not reach statistical significance.
These adipokine measurements were taken in mice after 28 days of HFD feeding with or without probiotic supplementation.
Results
Immune responses observed in the Caco-2/THP-1 co-culture model and in vivo were heterogeneous and depended on the experimental context.
A Caco-2/THP-1 co-culture model was used to evaluate immune responses to fermentation samples.
Immune responses varied depending on whether they were assessed in vitro or in vivo.
No single consistent immunomodulatory direction (pro- or anti-inflammatory) was observed across all experimental conditions.
The authors noted that immune responses depended on the experimental context.
Discussion
Direct SCFA-mediated causality between probiotic treatment, microbial fermentation changes, and host endocrine/metabolic responses remains to be established.
The study design did not allow for direct attribution of effects to SCFAs specifically.
Fermentation samples used in cell models contained a complex mixture of metabolites, not isolated SCFAs.
The authors stated that 'direct SCFA-mediated causality remains to be established.'
The findings were characterized as supporting a 'functional association' rather than proven causality.
What This Means
This research suggests that a specific probiotic strain called Lactiplantibacillus pentosus CECT 8039 may help counteract some of the harmful effects of a high-fat diet by changing how gut bacteria produce fermentation byproducts called short-chain fatty acids (SCFAs), and by influencing hormones involved in hunger and metabolism. In laboratory simulations of the human colon, the probiotic increased beneficial bacteria (like lactic acid bacteria), decreased potentially harmful bacteria (like Clostridium), and caused substantial increases in acetate, propionate, and butyrate — three key SCFAs. When gut cells were exposed to these fermentation products, they released more satiety-related hormones like GLP-1, PYY, and CCK, which are known to signal fullness to the brain.
In mice fed a high-fat diet for 28 days, those given the probiotic gained about 13% less body weight relative to control mice that did not receive it. The probiotic-supplemented mice also had dramatically lower blood levels of leptin (by about 85%) and resistin (by about 26%), both of which are hormones associated with obesity and metabolic dysfunction. However, changes in adiponectin — a hormone generally considered protective — were not statistically significant, and immune effects were inconsistent across different experimental settings.
This research suggests that this probiotic strain may help modulate the gut environment in ways that support healthier hormone signaling and slower weight gain in the context of a high-fat diet. However, the study cannot confirm that SCFAs alone caused these effects, since the fermentation samples used in cell experiments contained many other compounds. Further research is needed to clarify the exact mechanisms and to determine whether these findings translate to humans.
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Veciana-Galindo C, Núñez-Delegido E, González-Santos J, Agüera-Santos J, Navarro-López V, Alberola-Jordá I. (2026). Microbial metabolite-mediated modulation of enteroendocrine and immune pathways by Lactiplantibacillus pentosus CECT 8039 in early diet-induced obesity.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1882392