2. Academic Validation
  3. Gut microbiota carcinogen metabolism causes distal tissue tumours

Gut microbiota carcinogen metabolism causes distal tissue tumours

  • Nature. 2024 Aug;632(8027):1137-1144. doi: 10.1038/s41586-024-07754-w.
Blanka Roje # 1,  Boyao Zhang # 2,  Eleonora Mastrorilli 2,  Ana Kovačić 3,  Lana Sušak 1,  Ivica Ljubenkov 4,  Elena Ćosić 1,  Katarina Vilović 5,  Antonio Meštrović 6,  Emilija Lozo Vukovac 7,  Viljemka Bučević-Popović 4,  Željko Puljiz 6,  Ivana Karaman 5,  Janoš Terzić 8,  Michael Zimmermann 9 10
Affiliations

Affiliations

  • 1 Laboratory for Cancer Research, University of Split School of Medicine, Split, Croatia.
  • 2 Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
  • 3 Public Health Institute of Split and Dalmatia County, Split, Croatia.
  • 4 Department of Chemistry, University of Split Faculty of Science, Split, Croatia.
  • 5 Department of Pathology, University Hospital of Split, Split, Croatia.
  • 6 Department of Gastroenterology, University Hospital of Split, Split, Croatia.
  • 7 Department of Pulmonology, University Hospital of Split, Split, Croatia.
  • 8 Laboratory for Cancer Research, University of Split School of Medicine, Split, Croatia. janos.terzic@mefst.hr.
  • 9 Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. michael.zimmermann@embl.de.
  • 10 Molecular Medicine Partnership Unit (MMPU), University of Heidelberg and European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. michael.zimmermann@embl.de.
  • # Contributed equally.
PMID: 39085612 DOI: 10.1038/s41586-024-07754-w
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.

Figures
Products