Blanka Roje, Boyao Zhang, Eleonora Mastrorilli, Ana Kovačić, Lana Sušak, Ivica Ljubenkov, Elena Ćosić, Katarina Vilović, Antonio Meštrović, Emilija Lozo Vukovac, Viljemka Bučević-Popović, Željko Puljiz, Ivana Karaman, Janoš Terzić, Michael Zimmermann
{"title":"肠道微生物群致癌物质代谢导致远端组织肿瘤","authors":"Blanka Roje, Boyao Zhang, Eleonora Mastrorilli, Ana Kovačić, Lana Sušak, Ivica Ljubenkov, Elena Ćosić, Katarina Vilović, Antonio Meštrović, Emilija Lozo Vukovac, Viljemka Bučević-Popović, Željko Puljiz, Ivana Karaman, Janoš Terzić, Michael Zimmermann","doi":"10.1038/s41586-024-07754-w","DOIUrl":null,"url":null,"abstract":"Exposure to environmental pollutants and human microbiome composition are important predisposition factors for tumour development1,2. Similar to drug molecules, pollutants are typically metabolized in the body, which can change their carcinogenic potential and affect tissue distribution through altered toxicokinetics3. Although recent studies demonstrated that human-associated microorganisms can chemically convert a wide range of xenobiotics and influence the profile and tissue exposure of resulting metabolites4,5, the effect of microbial biotransformation on chemical-induced tumour development remains unclear. Here we show that the depletion of the gut microbiota affects the toxicokinetics of nitrosamines, which markedly reduces the development and severity of nitrosamine-induced urinary bladder cancer in mice6,7. We causally linked this carcinogen biotransformation to specific gut bacterial isolates in vitro and in vivo using individualized bacterial culture collections and gnotobiotic mouse models, respectively. We tested gut communities from different human donors to demonstrate that microbial carcinogen metabolism varies between individuals and we showed that this metabolic activity applies to structurally related nitrosamine carcinogens. Altogether, these results indicate that gut microbiota carcinogen metabolism may be a contributing factor for chemical-induced carcinogenesis, which could open avenues to target the microbiome for improved predisposition risk assessment and prevention of cancer. A study links environmental nitrosamines to bladder cancer through their metabolism by specific commensal microorganisms occurring in the gastrointestinal tract of humans and mice.","PeriodicalId":18787,"journal":{"name":"Nature","volume":null,"pages":null},"PeriodicalIF":50.5000,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41586-024-07754-w.pdf","citationCount":"0","resultStr":"{\"title\":\"Gut microbiota carcinogen metabolism causes distal tissue tumours\",\"authors\":\"Blanka Roje, Boyao Zhang, Eleonora Mastrorilli, Ana Kovačić, Lana Sušak, Ivica Ljubenkov, Elena Ćosić, Katarina Vilović, Antonio Meštrović, Emilija Lozo Vukovac, Viljemka Bučević-Popović, Željko Puljiz, Ivana Karaman, Janoš Terzić, Michael Zimmermann\",\"doi\":\"10.1038/s41586-024-07754-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Exposure to environmental pollutants and human microbiome composition are important predisposition factors for tumour development1,2. Similar to drug molecules, pollutants are typically metabolized in the body, which can change their carcinogenic potential and affect tissue distribution through altered toxicokinetics3. Although recent studies demonstrated that human-associated microorganisms can chemically convert a wide range of xenobiotics and influence the profile and tissue exposure of resulting metabolites4,5, the effect of microbial biotransformation on chemical-induced tumour development remains unclear. Here we show that the depletion of the gut microbiota affects the toxicokinetics of nitrosamines, which markedly reduces the development and severity of nitrosamine-induced urinary bladder cancer in mice6,7. We causally linked this carcinogen biotransformation to specific gut bacterial isolates in vitro and in vivo using individualized bacterial culture collections and gnotobiotic mouse models, respectively. We tested gut communities from different human donors to demonstrate that microbial carcinogen metabolism varies between individuals and we showed that this metabolic activity applies to structurally related nitrosamine carcinogens. Altogether, these results indicate that gut microbiota carcinogen metabolism may be a contributing factor for chemical-induced carcinogenesis, which could open avenues to target the microbiome for improved predisposition risk assessment and prevention of cancer. A study links environmental nitrosamines to bladder cancer through their metabolism by specific commensal microorganisms occurring in the gastrointestinal tract of humans and mice.\",\"PeriodicalId\":18787,\"journal\":{\"name\":\"Nature\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":50.5000,\"publicationDate\":\"2024-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.nature.com/articles/s41586-024-07754-w.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://www.nature.com/articles/s41586-024-07754-w\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature","FirstCategoryId":"103","ListUrlMain":"https://www.nature.com/articles/s41586-024-07754-w","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Gut microbiota carcinogen metabolism causes distal tissue tumours
Exposure to environmental pollutants and human microbiome composition are important predisposition factors for tumour development1,2. Similar to drug molecules, pollutants are typically metabolized in the body, which can change their carcinogenic potential and affect tissue distribution through altered toxicokinetics3. Although recent studies demonstrated that human-associated microorganisms can chemically convert a wide range of xenobiotics and influence the profile and tissue exposure of resulting metabolites4,5, the effect of microbial biotransformation on chemical-induced tumour development remains unclear. Here we show that the depletion of the gut microbiota affects the toxicokinetics of nitrosamines, which markedly reduces the development and severity of nitrosamine-induced urinary bladder cancer in mice6,7. We causally linked this carcinogen biotransformation to specific gut bacterial isolates in vitro and in vivo using individualized bacterial culture collections and gnotobiotic mouse models, respectively. We tested gut communities from different human donors to demonstrate that microbial carcinogen metabolism varies between individuals and we showed that this metabolic activity applies to structurally related nitrosamine carcinogens. Altogether, these results indicate that gut microbiota carcinogen metabolism may be a contributing factor for chemical-induced carcinogenesis, which could open avenues to target the microbiome for improved predisposition risk assessment and prevention of cancer. A study links environmental nitrosamines to bladder cancer through their metabolism by specific commensal microorganisms occurring in the gastrointestinal tract of humans and mice.
期刊介绍:
Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.