Mechanism of Lacticaseibacillus paracasei CCFM1321 in Regulating Intestinal Neural-Immune-Epithelial Barrier Interactions to Alleviate Cathartic Colon through Activation of the Propionic Acid-5-HT-ACh-GDNF-RET Signaling Pathway

Enteric glial cells (EGCs) are pivotal regulators of intestinal homeostasis, and their dysfunction is implicated in cathartic colon. This study investigated the efficacy and mechanism of Lacticaseibacillus paracasei CCFM1321 in alleviating this condition. A senna leaf extract-induced mouse model was employed, and constipation-related indices were evaluated following intervention with various L. paracasei strains. Among the tested strains, CCFM1321 most effectively improved gut motility and repaired the intestinal barrier. Mechanistically, CCFM1321 modulated the gut microbiota, increased propionic acid production, and subsequently enhanced 5-HT and acetylcholine levels. This neuroendocrine shift activated the GDNF-RET signaling pathway in EGCs, promoting enteric neuron function and epithelial integrity. Our findings elucidate a novel microbial-driven, EGC-mediated pathway for alleviating cathartic colon, highlighting CCFM1321 as a promising probiotic candidate for functional constipation.