Lactobacillus acidophilus alleviates slow transit constipation by modulating 5-HT pathway and gut microbial composition

Introduction Slow transit constipation (STC) is a chronic disease characterized by delayed intestinal transit and weakened spontaneous contractions of colonic smooth muscle. Current pharmacological treatments are often associated with adverse effects, highlighting the need for safe and more effective therapeutic strategies. This study investigated the potential role of Lactobacillus acidophilus ( L. acidophilus ) in regulating intestinal motility and alleviating STC, as well as the underlying mechanism. Methods A humanized mouse model was established by intragastric administration of fecal bacterial suspension from STC patients on alternate days, in order to evaluate the effect of L. acidophilus on constipation. The regulatory effect of L. acidophilus on intestinal motility was evaluated using defecation parameters. Colon histopathology was assessed by hematoxylin-eosin (H&E) staining. Immunohistochemistry (IHC), RT-qPCR, ELISA, and in vitro cell experiments were performed to examine the inflammatory cytokine levels and changes in the 5-hydroxytryptamine (5-HT) signaling pathway. In addition, metagenomic sequencing was used to analyze changes in the intestinal microbial community. Results The results showed L. acidophilus treatment significantly enhanced intestinal peristalsis and maintained the intestinal barrier by up-regulating Occludin expression and down-regulating inflammatory cytokines, including TNF-α and IL-1β , thereby suppressing inflammatory responses. Both in vivo and in vitro experiments showed that L. acidophilus affected the synthesis and release of 5-HT by regulating the expression of TPH1 and the mechanosensitive ion channel Piezo1 . Additionally, L. acidophilus reshaped the intestinal microbial community structure and altered the inter-bacterial interaction network, which was closely associated with improved intestinal motility. Conclusion Our current research reveals that constipation symptoms by L. acidophilus through the gut microbiota composition, intestinal barrier, and the 5-HT signaling pathway. These findings provide a strong theoretical basis for the development of L. acidophilus as a potential therapeutic strategy for the treatment of STC.