Gut microbiota carcinogen metabolism causes distal tissue tumours

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 () and Michael Zimmermann ()
Additional contact information
Blanka Roje: University of Split School of Medicine
Boyao Zhang: European Molecular Biology Laboratory
Eleonora Mastrorilli: European Molecular Biology Laboratory
Ana Kovačić: Public Health Institute of Split and Dalmatia County
Lana Sušak: University of Split School of Medicine
Ivica Ljubenkov: University of Split Faculty of Science
Elena Ćosić: University of Split School of Medicine
Katarina Vilović: University Hospital of Split
Antonio Meštrović: University Hospital of Split
Emilija Lozo Vukovac: University Hospital of Split
Viljemka Bučević-Popović: University of Split Faculty of Science
Željko Puljiz: University Hospital of Split
Ivana Karaman: University Hospital of Split
Janoš Terzić: University of Split School of Medicine
Michael Zimmermann: European Molecular Biology Laboratory

Nature, 2024, vol. 632, issue 8027, 1137-1144

Abstract: 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.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-07754-w Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:632:y:2024:i:8027:d:10.1038_s41586-024-07754-w

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-07754-w

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().