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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&amp;E histopathological scores (p &lt; 0.05). It also reduced the serum levels of pro-inflammatory cytokines, including IL-6, IL-1\u03b2, TNF-\u03b1, and malondialdehyde (p &lt; 0.01), increased the levels of the anti-inflammatory factor IL-10 (p &lt; 0.001) and antioxidant enzymes SOD and GSH-Px (p &lt; 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 &lt; 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-1\u03b2. 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.<\/jats:p>","DOI":"10.3390\/nu18193199","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:35:59Z","timestamp":1790595359000},"page":"3199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heat-Inactivated Lacticaseibacillus paracasei PC-01 Alleviates DSS-Induced Colitis in Mice by Modulating Gut Microbiota and Intestinal Barrier Function"],"prefix":"10.3390","volume":"18","author":[{"given":"Xinxue","family":"Zhao","sequence":"first","affiliation":[{"name":"Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Key Laboratory of Dairy Products 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China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"given":"Hongxia","family":"Liu","sequence":"additional","affiliation":[{"name":"Inner Mongolia Mengniu Dairy (Group) Co., Ltd., Hohhot 011500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Zhihong","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Guohong","family":"Wang","sequence":"additional","affiliation":[{"name":"Inner Mongolia Mengniu Dairy (Group) Co., Ltd., Hohhot 011500, China"},{"name":"Mengniu Hi-Tech Dairy Products (Beijing) Co., Ltd., Beijing 101100, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Feiyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Hohhot 010018, 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