{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T14:50:11Z","timestamp":1777906211518,"version":"3.51.4"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Inflammatory bowel disease (IBD) is a chronic autoimmune disorder driven by gut microbiota dysbiosis. As an essential immune checkpoint, Programmed death-ligand 1 (PD-L1) has been implicated in modulating gut microbiota composition. However, the precise role of PD-L1 in shaping metagenomic profiles during IBD-associated colitis remains unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DSS-induced colitis was established in both PD-L1 knockout (<jats:italic>Pdcd1lg1-\/-<\/jats:italic>) mice and wild-type (wt) control mice. Clinical parameters, including disease activity index (DAI), body weight changes, colon length, and histopathological alterations, were systematically evaluated using non-parametric Kruskal-Wallis tests and ANOVA to compare colitis severity between genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PD-L1 knockout mice exhibited exacerbated colitis, manifesting significantly greater weight loss (p&amp;lt;0.05 vs. wt_DSS), colonic shortening (p&amp;lt;0.05), and DAI scores (p&amp;lt;0.05) and inflammatory changes. PD-L1 knockout mice showed distinct dysbiosis, with enriched pathobionts (<jats:italic>Escherichia coli<\/jats:italic>, p=0.006; <jats:italic>Bacteroides thetaiotaomicron<\/jats:italic>, p=0.015) and depletion of commensals (<jats:italic>Tritrichomonas foetus<\/jats:italic>, p&amp;lt;0.001; <jats:italic>Ligilactobacillus murinus<\/jats:italic>). Alpha diversity analysis using Chao1 index revealed statistically significant differences between experimental groups (p=0.05). The transporters downregulate anti-inflammatory SCFA metabolism. KEGG enrichment analysis of differentially expressed genes (DEGs) revealed significant associations with immune and inflammatory pathways in PD-L1 knockout mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PD-L1 deficiency aggravates colitis by driving pathogenic microbiota alterations and impairing microbial metabolic homeostasis, highlighting its dual regulatory roles in immune homeostasis and microbiome dynamics.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1622744","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T05:26:14Z","timestamp":1751261174000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["PD-L1 deficiency exacerbates colitis severity by remodeling gut microbiota in inflammatory bowel 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