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.

Constipation is a prevalent gastrointestinal disorder that severely affects people's daily life and work. Bifidobacterium has been proven to be effective in relieving constipation. Compared with single-strain intervention, the combined intervention of probiotics and oligosaccharides can produce more significant health effects. However, its specific efficacy and mechanism in relieving constipation have not been fully elucidated. This study aims to explore the potential of the synergistic intervention of Bifidobacterium and oligosaccharides in improving constipation, with a particular emphasis on investigating the regulatory effects of the combined intervention on the gut microbiota and its metabolites. In this study, based on the physiological characteristics of the strains and animal experiments, a strain of B. longum CCFM760 capable of relieving constipation was screened. Furthermore, nine kinds of oligosaccharides were used to replace glucose as the single carbon source respectively. According to the shortest generation time of the strain, lactulose was selected as the compounding factor to investigate how the combined intervention of B. longum CCFM760 and lactulose relieves constipation and reveal the involved mechanisms. It was shown that compared with the single-strain intervention, the combined intervention therapy could better relieve constipation. By promoting the intestinal colonization of Bifidobacterium, it could more significantly reduce the relative abundances of harmful bacteria such as Bilophila and Negativibacillus, and at the same time significantly enrich short-chain fatty acids (SCFAs)-producing bacteria such as Bifidobacterium, Faecalibaculum, and Ileibacterium. Therefore, it could more effectively restore the levels of SCFAs in the gut, increase the expression level of serotonin 4 receptor (5-HT4R), improve the levels of gastrointestinal active peptides (increasing the levels of gastrin (GAS) and motilin (MTL), and decreasing the level of vasoactive intestinal peptide (VIP)), as well as the expression levels of calcitonin gene-related peptide (CGRP) and brain derived neurotrophic factor (BDNF), and reduce the expressions of Aquaporin-3 (AQP3) and inducible nitric oxide synthase (iNOS) in the colon tissue, thus more effectively relieving constipation. These results lay the foundation for the development of dietary formula foods with the efficacy of relieving constipation.

Intestinal motility disorders represent a significant pathological feature of various gastrointestinal conditions, involving intricate interactions among the enteric nervous system (ENS), microbial communities, and the immune system. Antibiotic usage disrupts this delicate balance, leading to intestinal motility disorders. To address this issue, the present study was based on the antibiotic-induced intestinal motility disorders mouse model, and interventions were performed using Bifidobacterium bifidum BB1, BB7, BB8, and CCFM1391. Our findings demonstrate that CCFM1391 significantly reduces intestinal transit time and fecal water content, which ameliorates abnormal intestinal motility (P < 0.01). It was shown that Bifidobacterium bifidum CCFM1391 had the most significant effect in regulating intestinal motility disorders, and therefore was selected as the subject for further investigation. Further exploration of its mechanism of action revealed that CCFM1391 adjusted the structure of intestinal flora (significantly increased the abundance of Akkermansia) (P < 0.0001), enhances short-chain fatty acids (SCFAs) production (acetic acid, propionic acid, isovaleric acid) (P < 0.05), and stimulates serotonin (5-HT) release (P < 0.0001), thereby activating the 5-HT₄ receptor pathway to restore enteric nerve function. Additionally, CCFM1391 strengthens the intestinal barrier by upregulating tight junction proteins (Occludin, Claudin-1, ZO-1) (P < 0.01) and modulating inflammatory responses—reducing pro-inflammatory factors (CXCL-1, IL-17) and increasing anti-inflammatory factors (TGF-β) (P < 0.01). These results underscore CCFM1391's efficacy in alleviating antibiotic-induced intestinal motility disorders through modulation of gut microbiota and their metabolites, and by influencing neuro-epithelial-immune interactions. This study provides a theoretical basis for probiotic interventions and highlights their potential clinical applications.