Lactiplantibacillus plantarum NCHBL-004 improves intestinal motility and modulates serotonergic gene expression in a loperamide-induced constipation model.

Slow-transit constipation (STC) is characterized by reduced colonic motility, impaired smooth muscle function, and altered mucosal signaling. Among these pathways, mucosal serotonin (5-HT), mainly produced by enterochromaffin cells, contributes to intestinal motility regulation. In a loperamide-induced constipation model in male C57BL/6 J mice, we evaluated the effects of Lactiplantibacillus plantarum NCHBL-004 on bowel function and associated molecular changes. Compared with loperamide-treated mice, live NCHBL-004 at 1 × 10⁹ CFU improved fecal output and gastrointestinal transit and partially preserved fecal water content, whereas the lower live dose and heat-killed preparation showed no significant effects. These functional changes were accompanied by preservation of colonic muscularis thickness and increased expression of smooth muscle-associated markers, including Acta2 and Myh11. NCHBL-004 also modulated mucosal serotonergic gene expression, as indicated by increased Tph1, which encodes a key enzyme for 5-HT synthesis, and decreased Slc6a4, which encodes the serotonin transporter involved in 5-HT reuptake. Overall, these findings suggest that live NCHBL-004 improves intestinal motility in loperamide-induced constipation, with associated changes in colonic smooth muscle phenotype and mucosal serotonergic regulation.