Heat-Inactivated Lacticaseibacillus paracasei PC-01 Alleviates DSS-Induced Colitis in Mice by Modulating Gut Microbiota and Intestinal Barrier Function

Background: Inflammatory bowel disease (IBD) is a chronic, progressive, immune-mediated inflammatory disorder of the gastrointestinal tract. Methods: This study used C57BL/6J mice induced by DSS to construct an intestinal inflammation model, and explored the alleviating effect and potential mechanism of heat inactivated Lactobacillus paracasei PC-01 (PC-01) on intestinal inflammation. Results: The results showed that heat-inactivated PC-01 significantly decreased the Disease Activity Index and H&E histopathological scores (p < 0.05). It also reduced the serum levels of pro-inflammatory cytokines, including IL-6, IL-1β, TNF-α, and malondialdehyde (p < 0.01), increased the levels of the anti-inflammatory factor IL-10 (p < 0.001) and antioxidant enzymes SOD and GSH-Px (p < 0.01), and restored the integrity of the intestinal epithelial barrier in DSS-induced colitis mice. Metagenomic analysis showed that PC-01 treatment restored the abundance of beneficial bacteria, including Barnesiella and Muribaculum, and reduced the enrichment of opportunistic pathogens such as Angelakisella and Lawsonibacter (p < 0.05). Further functional annotation of the microbial community indicated that PC-01 significantly enriched pathways related to the TCA cycle, riboflavin metabolism, Toll and Imd signaling, and lipopolysaccharide biosynthesis. In addition, the relative abundances of auxiliary activities, polysaccharide lyases, and S-layer homology modules were lower than those in the DSS group, whereas those of glycoside hydrolases, glycosyltransferases, and carbohydrate esterases were higher. At the transcriptional level, intervention with heat-inactivated PC-01 resulted in a downward trend in the expression of TLR4, Nfkb1, and Rela, accompanied by reduced expression of the chemokines MCP-1 and Cxcl10, and inflammasome-related genes NLRP3, Casp1, and IL-1β. Conclusions: In summary, heat-inactivated Lacticaseibacillus paracasei PC-01 effectively alleviated intestinal inflammatory injury in mice by regulating gut microbiota homeostasis and suppressing intestinal inflammatory responses.