The gut microbiota metabolism of environmental carcinogens promotes the development of a chemically induced cancer

Roje B, Zhang B, Mastrorilli E, et al. Gut microbiota carcinogen metabolism causes distal tissue tumours. Nature 2024; doi: 10.1038/s41586-024-07754-w.

The human gut bacteria metabolise carcinogens and distribute them to distal tissues, but the contribution of the gut microbiota to tumourigenesis remains unclear. Roje et al. investigated the effect of gut microbiota on the development of a chemically induced tumour, bladder cancer. Antibiotic oral administration on mice with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), a nitrosamine compound, induced bladder cancer, which led to a reduced prevalence and severity of tumourigenesis. The abundance of N-butyl-N-(3-carboxypropyl)-nitrosamine (BCPN), a cancer-inducing host BBN metabolite, was also found at a reduced level at both urothelium and caecum following the antibiotic treatment.

Based on the metabolomics, Roje et al found β-glucuronidases of the gut microbiota deconjugate a BBN derivative, glucuronidated BBN (gBBN), to liberate BBN for elevated BCPN synthesis by the host. Alternatively, the gut microbiota also has the metabolic capacity to directly oxidise BBN to BCPN as the incubation of ex vivo microbiota cultures with BBN resulted in the synthesis of BCPN. Seven BBN-converting bacteria isolates spanning Escherichia, Enterococcus and Haemophilius were found at a detectable level in the human faecal community. Mono-colonisation of Escherichia flexneri, a representative human BBN-metabolising bacterium, in the germ-free mice led to BCPN accumulation in the lower intestine. BBN-treated germ-free mice inoculated with non-BBN-metabolising bacteria did not metabolise BBN in contrast to those inoculated with BBN-metabolising bacteria. The toxicokinetics of other nitrosamine carcinogens were similarly altered by the gut microbiota.

In summary, this study demonstrated the effect of gut microbiota on the toxicokinetics of carcinogens and hence promoted the development of a chemically induced bladder cancer on mice.

A unique serum IgG glycosylation signature predicts development of Crohn’s disease and is associated with pathogenic antibodies to mannose glycan

Gaifem J, Rodrigues C, Petralia F, et al. A unique serum IgG glycosylation signature predicts development of Crohn’s disease and is associated with …