Lacticaseibacillus rhamnosus LRPerfectus158 Alleviates Postinfectious Irritable Bowel Syndrome in Mice and Is Associated With Modulation of Hypothalamic–Pituitary–Adrenal Axis Activity

ABSTRACT Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder marked by chronic low‐grade inflammation, heightened visceral sensitivity, and disruptions in gut microbiota composition. In this study, the alleviating effects and underlying mechanism of Lacticaseibacillus rhamnosus LRPerfectus158 was investigated using an IBS mouse model established through Citrobacter rodentium infection followed by water‐avoidance stress. LRPerfectus158 administration significantly alleviated IBS‐like symptoms, including reduced fecal moisture content, restored colon length, and attenuated visceral hypersensitivity. Behavioral assessments further showed that LRPerfectus158 alleviated anxiety‐like behaviors. Moreover, LRPerfectus158 administration decreased serum corticosterone levels, accompanied by reduced hippocampal injury, suggesting a potential association with altered hypothalamic–pituitary–adrenal (HPA) axis activity. Colonic histology and molecular analyses revealed that LRPerfectus158 mitigated inflammation, increased goblet cell abundance, and enhanced epithelial barrier integrity by upregulating ZO‐1 and MUC2 at both mRNA and protein levels. Transcriptomic profiling further confirmed the dual effects of LRPerfectus158 in IBS, demonstrating its ability to alleviate intestinal neural hypersensitivity while concurrently suppressing mucosal inflammation and strengthening epithelial barrier integrity. Metagenomic sequencing showed that LRPerfectus158 was associated with alterations in gut microbiota composition, including increased relative abundances of taxa such as Muribaculum , Duncaniella , Bacteroides uniformis , and Ligilactobacillus murinus . Collectively, these findings suggest that LRPerfectus158 is associated with alleviation of IBS‐like symptoms, correlating with modulation of the gut microbiota, reinforcement of the intestinal barrier, and reduced HPA axis hyperactivation, which highlights its potential as a promising probiotic candidate for IBS intervention.