{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:25:06Z","timestamp":1787030706683,"version":"build-2736575974"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The gut microbiome has emerged as a potential modulator of transplant rejection. However, the relevance of anaerobe-associated gut microbial communities to transplant rejection responses remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a murine islet transplantation model, we assessed the effects of metronidazole pretreatment on allograft survival and function. 16S rRNA sequencing was performed to characterize treatment-associated changes in gut microbial composition. Separately, an exploratory two-sample MR analysis using human GWAS data was performed to prioritize gut microbial taxa associated with a composite outcome of transplant failure or rejection. Biological annotation was subsequently used to prioritize candidate host pathways. Immunohistochemistry and flow cytometry were used to evaluate post-transplant immune responses after metronidazole pretreatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Metronidazole treatment remodeled gut microbiota composition and significantly delayed islet allograft rejection. MR analyses identified several anaerobe-associated gut microbial taxa potentially relevant to transplant rejection risk, including the family\n                      <jats:italic>Defluviitaleaceae<\/jats:italic>\n                      and the genera\n                      <jats:italic>Intestinibacter<\/jats:italic>\n                      ,\n                      <jats:italic>Bilophila<\/jats:italic>\n                      ,\n                      <jats:italic>Ruminococcus<\/jats:italic>\n                      and\n                      <jats:italic>Eubacterium fissicatena<\/jats:italic>\n                      . Integrative biological annotation highlighted glycosylation-related pathways and prioritized ST3GAL4 for subsequent expression assessment in the murine transplant model. Furthermore, metronidazole treatment reduced CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell infiltration around the allograft and Th17-related inflammatory responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Altogether, our findings document gut microbial remodeling and delayed allograft rejection following metronidazole pretreatment. These findings are hypothesis-generating and warrant further mechanistic investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1874387","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:28:34Z","timestamp":1787027314000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Metronidazole-mediated gut anaerobe remodeling is associated with transplant rejection"],"prefix":"10.3389","volume":"16","author":[{"given":"Yanzhuo","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Oncology, The Affiliated Hospital of Southwest Jiaotong University, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]},{"name":"Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Tian","sequence":"additional","affiliation":[{"name":"Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlan","family":"Pu","sequence":"additional","affiliation":[{"name":"Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhao","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Hospital of Southwest Jiaotong University, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Hospital of Southwest Jiaotong University, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Hospital of Southwest Jiaotong University, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongke","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Hospital of Southwest Jiaotong University, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yuan","sequence":"additional","affiliation":[{"name":"The Seventh People\u2019s Hospital of Chengdu Affiliated Cancer Hospital of Chengdu Medical College","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Hospital of Southwest Jiaotong University, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1053\/j.ajkd.2004.04.040","article-title":"Late urinary tract infection after renal transplantation in the United States","volume":"44","author":"Abbott","year":"2004","journal-title":"Am. 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