{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T19:33:59Z","timestamp":1788550439601,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,23]],"date-time":"2021-10-23T00:00:00Z","timestamp":1634947200000},"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","award":["81872555, 81803062, 82003399 and 81730086"],"award-info":[{"award-number":["81872555, 81803062, 82003399 and 81730086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019539","name":"Science Foundation for Distinguished Young Scholars of Tianjin","doi-asserted-by":"publisher","award":["20JCJQJC00100"],"award-info":[{"award-number":["20JCJQJC00100"]}],"id":[{"id":"10.13039\/501100019539","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived l-Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of l-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. l-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. l-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of l-Histidine, accumulated in peripheral blood and lung tissues following l-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced l-Histidine and ImP are promising radioprotective agents.<\/jats:p>","DOI":"10.3390\/ijms222111436","type":"journal-article","created":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T22:06:16Z","timestamp":1635113176000},"page":"11436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Gut Microbiota-Derived l-Histidine\/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury"],"prefix":"10.3390","volume":"22","author":[{"given":"Zhiyuan","family":"Chen","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Dong","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhou","family":"Zeng","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwen","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saijun","family":"Fan","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Cui","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1001\/jamaoncol.2019.0086","article-title":"Treatment-Related Complications of Systemic Therapy and Radiotherapy","volume":"5","author":"Jairam","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1056\/NEJMra1608986","article-title":"Recent Developments in Radiotherapy","volume":"377","author":"Citrin","year":"2017","journal-title":"N. 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