Introduction

Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, is characterized by chronic intestinal inflammation linked to dysbiosis and impaired bile acid (BA) metabolism. Recent studies have underscored the pivotal role of the gut microbiota–BA axis in modulating intestinal immunity [1]. Disruptions in this axis, particularly reduced microbial conversion of primary to secondary BAs, have been implicated in the pathogenesis of IBD [2–4]. Probiotic interventions have emerged as promising strategies to restore microbial balance and modulate BA profiles. Some probiotic bacteria express enzymes that can modify bile acids thereby influencing BA receptor signaling pathways such as GPBAR1, FXR and receptors that have recently been identified as BA-binding receptors, such as RORγt [4–6]. Building upon this framework, our previous research demonstrated that specific microbial-derived BAs, notably 3-oxo-DCA, act as dual agonists for GPBAR1 and inverse agonists for RORγt, leading to reduced Th17-mediated inflammation in murine models of colitis [7]. These findings suggest that targeted modulation of the gut microbiota–BA axis via probiotic formulations could offer therapeutic benefits in IBD management.

Aims & Methods

To investigate the therapeutic potential of a novel multi-strain probiotic formulation in reducing colitis. For this purpose, we employed murine models of colitis induced in male C57BL/6 mice. In the acute colitis model, disease was induced by administering a 2% dextran sulfate sodium (DSS) solution in drinking water for 9 days. Chronic colitis was induced using three cycles of 1.5% DSS administration (1 week) followed by 15 days of water to mimic the exacerbation-remission phases of human IBD. The new probiotic formulation, named Vivomixx neo9®, was administered daily by gavage at 50 × 10^9 CFU/kg. Vivomixx neo9® included nine bacterial strains: Bifidobacterium animalis subsp. lactis, Bifidobacterium breve, Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus rhamnosus (two distinct bacterial strains), Lactobacillus lactis, and Streptococcus thermophilus. Vivomixx®, a commercial probiotic, served as the control.

Results

Our data demonstrated that treatment with both probiotic strains effectively mitigated disease severity in both acute and chronic murine models of colitis. Furthermore, the novel probiotic formulation notably ameliorated colonic mucosal injury at both macroscopic and microscopic levels and decreased fibrosis indices. DSS administration induced severe gut dysbiosis, reflected by substantial alterations in intestinal microbiota composition and disrupted BA profiles. Specifically, fecal BA analysis revealed a pronounced dysregulation characterized by diminished secondary BA levels and an elevated primary-to-secondary BA ratio. Probiotic treatment effectively reversed these dysbiotic changes, restoring fecal BA profiles comparable to those observed in naive mice. Of particular interest, the novel multi-strain probiotic enhanced the generation of oxo- and allo-BA derivatives, recognized as dual agonists for GPBAR1 and inverse agonists for RORγt, regulators of innate and adaptive immune responses.

Conclusion

Our findings indicate that Vivomixx neo9® significantly reduces colitis severity through modulation of intestinal microbiota composition and normalization of fecal bile acid profiles. These results underscore the therapeutic promise of targeting microbiota–bile acid interplay as a supplementary approach in the clinical management of IBD.

References

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