{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:12:46Z","timestamp":1793812366351,"version":"4.6.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"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. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n Dysbiosis of gut bacteria has been discovered in a large number of autoimmune diseases. However, the influence of the gut bacteria in the mice model of chronic sclerodermatous graft-versus-host disease (Scl-GVHD), a disease that resembles an autoimmune disease characterized by chronic inflammation of multiple organs, such as skin, remains elusive. Here, we explore the role of gut bacteria in an Scl-cGVHD mice model.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We established a mouse model of Scl-cGVHD, collected fecal flora, analyzed the composition, and diversity of intestinal flora using 16S rDNA amplicon sequencing, and detected the proportion of Treg and Th1 cells in splenocytes of Scl-cGVHD mice. To verify the immunoregulatory effect of Scl-cGVHD intestinal flora, we prepared bacterial extracts, co-cultured with splenocytes\n in vitro<\/jats:italic>\n , and used flow cytometry to detect T cell differentiation and cytokine secretion.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n By examining T-cell differentiation in splenocytes of cGVHD mice, we found that Treg cells were significantly reduced (15.27 \u00b1 0.23 vs. 12.23 \u00b1 0.47,\n p<\/jats:italic>\n = 0.0045) and Th1 cells were increased (1.54 \u00b1 0.18 vs. 6.68 \u00b1 0.80,\n p<\/jats:italic>\n = 0.0034) in cGVHD mice. Significant differences were observed in the composition and diversity of the gut bacteria in mice with Scl-cGVHD versus without GVHD. Analysis of mice fecal bacteria samples (\n n<\/jats:italic>\n = 10, 5 Scl-cGVHD and 5 Non-GVHD) showed significant separation [\n R<\/jats:italic>\n = 0.732,\n p<\/jats:italic>\n = 0.015, non-parametric analysis (ANOSIM)] in Scl-cGVHD and non-GVHD mice. The abundance of the family and genus\n Ruminococcaceae<\/jats:italic>\n bacteria decreased and the family\n Lachnospiraceae<\/jats:italic>\n and limited to the species\n Lachnospiraceae_bacterium_DW17<\/jats:italic>\n increased in Scl-cGVHD mice.\n In vitro<\/jats:italic>\n results of the cellular level study suggest that the bacteria extracts of gut microbiota from Scl-cGVHD mice modulated the splenic T cells toward differentiation into CD4\n +<\/jats:sup>\n IFN-\u03b3\n +<\/jats:sup>\n Th1 cells (14.37 \u00b1 0.32 vs. 10.40 \u00b1 2.19,\n p<\/jats:italic>\n = 0.036), and the percentage of CD4\n +<\/jats:sup>\n CD25\n +<\/jats:sup>\n Foxp3\n +<\/jats:sup>\n Tregs decreased (6.36 \u00b1 0.39 vs. 8.66 \u00b1 0.07,\n p<\/jats:italic>\n = 0.001) compared with the non-GVHD mice. In addition, the secretion of proinflammatory interferon- \u03b3 (IFN-\u03b3) cytokine in the supplement of cellular culture was increased (4,898.58 \u00b1 235.82 vs. 4,347.87 \u00b1 220.02 pg\/ml,\n p<\/jats:italic>\n = 0.042) in the mice model of the Scl-cGVHD group, but anti-inflammatory interleukin (IL)-10 decreased (7,636.57 \u00b1 608.05 vs. 9,563.56 \u00b1 603.34 pg\/ml,\n p<\/jats:italic>\n = 0.018).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our data showed the different composition and diversity of gut bacteria in the Scl-cGVHD mice. The dysbiosis of gut bacteria may regulate the differentiation ratio of Treg and Th1 cells, which was associated with Scl-cGVHD.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2022.813576","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T03:09:09Z","timestamp":1662606549000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["The Gut Bacteria Dysbiosis Contributes to Chronic Graft-Versus-Host Disease Associated With a Treg\/Th1 Ratio Imbalance"],"prefix":"10.3389","volume":"13","author":[{"given":"Yulian","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suxia","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilong","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyu","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13045-018-0586-4","article-title":"Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT.","volume":"11","author":"Annalisa","year":"2018","journal-title":"J. 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