What is already known
Growing evidence suggests that the human microbiota can influence cancer development and progression either by travelling to tissues and producing cancer-causing compounds or by metabolizing drugs and other substances. But it’s unclear whether gut microbes can influence cancer development by metabolizing environmental carcinogens such as chemicals found in cigarette smoke.
What this research adds
Researchers induced bladder cancer in mice by exposing the animals to the nitrosamine BBN, one of the chemicals found in tobacco smoke. Depleting the gut microbiota reduced cancer incidence. Further tests showed that gut bacteria can convert the nitrosamine BBN into another nitrosamine, called BCPN, which accumulates in the bladder and induces tumors. The researchers identified 12 species capable of this transformation, many of which typically reside on the skin. Bacteria from human fecal samples could also convert BBN to BCPN when transferred into germ-free mice.
Conclusions
The findings suggest that the microbiota processes environmental carcinogens in ways that lead to cancer.
Carcinogens are chemicals found in various sources, including tobacco smoke, that can cause normal cells to change into cancerous ones. Now, a study in mice suggests that the microbiota processes environmental carcinogens in ways that lead to cancer.
The findings, published in Nature, highlight the potential for microbiota-targeted strategies in cancer risk assessment and prevention.
“We think this lays the foundation for further research to see whether a person’s gut microbiome represents a predisposition for chemically induced carcinogenesis and could hence be used to predict the individual risk and potentially prevent cancer development,” says study co-author Michael Zimmermann at the European Molecular Biology Laboratory in Heidelberg, Germany.
Growing evidence suggests that the human microbiota can influence cancer development and progression either by travelling to tissues and producing cancer-causing compounds or by metabolizing drugs and other substances. But it’s unclear whether gut microbes can influence cancer development by metabolizing environmental carcinogens such as chemicals found in cigarette smoke.
To examine this phenomenon, Zimmermann and his colleagues induced bladder cancer in mice by exposing the animals to the nitrosamine BBN, one of the chemicals found in tobacco smoke.
Bio-transformation
Treating mice with antibiotics to deplete their gut microbiota reduced cancer incidence, the researchers found. After exposure to BBN, 81% of mice that received antibiotics had no bladder tumors, whereas 77% of mice that weren’t treated with antibiotics developed early tumors and 53% had more invasive tumors.
Further tests showed that gut bacteria can convert the nitrosamine BBN into another nitrosamine, called BCPN. This compound traveled to the bladder of mice and accumulated there, where it induced tumors.
After studying more than 500 bacterial strains, the research identified 12 species capable of transforming BBN into BCPN. Many of these microbes typically reside on the skin and are found in low abundance in the gut, suggesting that the bacteria move from the skin to the gut as the animals groom themselves.
Carcinogen metabolism
Bacteria from human fecal samples could also convert BBN to BCPN when transferred into germ-free mice, the researchers found. However, people’s gut bacteria vary widely in how well they can process BBN, and the types of bacteria involved in this process also differ from person to person.
“This difference in inter-individual microbiota could explain why some people, despite being exposed to potential carcinogens, do not develop cancers while others do,” says study co-author Janoš Terzić at the University of Split School of Medicine in Croatia.
The findings suggest that the metabolism of environmental carcinogens by the gut microbiota plays a role in cancer, but more work is needed to understand how gut bacteria affect the breakdown of various cancer-causing chemicals, the researchers say.
