Bifidobacterium bifidum CCFM1163 Alleviates Cathartic Colon Through the Acetate/Propionate-GPR41-Gβγ Pathway

Abstract

Cathartic colon, a form of slow-transit constipation, arises from prolonged stimulant laxative use and is associated with intestinal barrier impairment and enteric nervous system damage. We identified Bifidobacterium bifidum CCFM1163 as an effective agent for alleviating cathartic colon; however, the underlying mechanisms remain unclear. This study first administered live, dead, and supernatant forms of CCFM1163 to cathartic colon mice, finding that only live bacteria were effective. Non-targeted and targeted metabolomics analyses of mouse fecal metabolites highlighted short-chain fatty acids (SCFAs) as key players. Animal experiments comparing the effects of major SCFAs revealed that acetic acid (AA) and propionic acid (PA) ameliorated cathartic colon (reduces intestinal transit time, p < 0.0001; increases fecal water content, p < 0.05). Inhibition studies using SCFAs receptor inhibitors and downstream inhibitors demonstrated that both HAS (a G protein-coupled receptor 41 [GPR41] inhibitor) and Gallein (Gi protein βγ subunit [Gβγ] inhibitor) negated the reparative effects of CCFM1163 on the enteric nerves and intestinal barrier in cathartic colon mice. CCFM1163 was shown to modulate the intestinal flora, notably increasing Faecalibaculum, Candidatus Saccharimonas, and Prevotellaceae UCG-001 (p < 0.05) and decreasing Escherichia, Clostridioides (p < 0.0001), while elevating AA and PA levels (p < 0.05). AAs act on the GPR41 receptor, activating the Gβγ, thus enhancing the intestinal barrier and reducing tissue inflammation. PA primarily repairs enteric nerves via GPR41-Gβγ, promoting peristalsis. This study elucidates B. bifidum CCFM1163's potential mechanisms in cathartic colon relief and provides a theoretical basis for probiotic treatment.