Nature finds gut bacteria process cancer-promoting molecules, remotely inducing cancer
International Business Department Liu Bojia August 02, 2024
The occurrence of cancer is related to many factors, from the molecular level may come from a variety of gene mutations or genetic damage, when the mutation of proto-oncogenes to promote cell proliferation, or oncogenes are damaged, losing the ability to regulate the cell cycle, will form the basis of the occurrence of cancer. In addition, the influence of external conditions should not be underestimated, especially when certain environmental pollutants enter the human body, they may directly or indirectly through metabolism form some conditions that promote the occurrence of cancer and accelerate the formation of tumours.
In today's issue of Nature, scientists from the University of Split, Croatia, in collaboration with the European Molecular Biology Laboratory (EMBL), have found that the intestinal flora, which live in harmony within our intestines, can become a cancer-promoting culprit, metabolising specific pollutants to produce new cancer-promoting substances that can be spread to tissues, increasing the risk of cancer.
We've probably heard a lot about the benefits of gut flora, such as their ability to break down dietary fibre, reduce gut inflammation and provide micronutrient molecules, and the ability of some flora to help clear tumours and enhance the effectiveness of immunotherapy. But gut bacteria also have two sides to them: when inflammation occurs in the gut, certain tumour-inducing microbes can leave the gut and enter other tissues to produce genotoxins that induce cellular carcinogenesis, and they also have the potential to metabolise and transform numerous foreign compound molecules.
The new study focuses on the process of bladder cancer, which has been linked to exposure to BBN, a nitrosamine-like molecule from tobacco mist, and which was effectively induced in mice in animal studies by prolonged exposure to BBN. This time, the authors tweaked things a little bit by giving some of the mice a full antibiotic treatment before the BBN treatment, which cleared out 99.99 per cent of the bacteria in the mice's intestines.
They were then co-exposed to BBN conditions with control mice for 12 weeks. Surprisingly, 81% of the mice in which the antibiotic treatment was executed in advance did not develop any pathological features of bladder tumours, whereas 77% of the control group underwent tumourisation of the bladder tissue, with a significant proportion of them having more aggressive tumour features.
Strictly speaking, it is the oxidative metabolite of BBN, BCPN, that undergoes bladder pro-carcinogenic effects upon entry into the body, and the latter is often enriched in the bladder and can form pro-carcinogenic DNA adducts with the DNA of bladder epithelial cells. The authors found that the gut happens to be the largest producer of BCPN, and that the antibiotic-treated mice had dramatically reduced levels of BCPN in the gut compared to controls, which also reduced the risk of BCPN scourging bladder epithelial cells.
With these findings, the authors were almost certain that the lost gut bacteria were the helpers in the conversion of BNN to BCPN! They immediately set about analysing the intestinal flora of more than 500 mice, and showed that there were a number of different subgroups that promoted the oxidation of BBN, involving eight genera such as Escherichia, Lactobacillus, and Staphylococcus.
In addition to this, this BNN-BNCP transition process is not only present only in mice, but the authors initially found in microbial culture tests extracted from human faecal samples that human Escherichia coli also possesses the ability to produce BCNP, and that this ability is more conserved across strains of different population origins. In particular, the conversion of BNN to BCPN was more efficient under microaerobic conditions.
The paper notes that these results provide a clearer understanding of the role of gut microbes in the development of cancer, as well as a completely new pathway for environmental molecules to cause cancer when they enter the body. And by testing the microbiome of individuals, it is also possible to determine whether they are more susceptible to specific environmental pollutants, helping more people to access cancer prevention strategies or even adjuvant tumour treatments that work for them.