Editors' ChoiceCancer

Beware! Are bacteria raising your oxidative stress?

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Science Translational Medicine  22 Feb 2017:
Vol. 9, Issue 378, eaam6066
DOI: 10.1126/scitranslmed.aam6066

Abstract

Peptostreptococcus anaerobius, enriched in patients with colon cancer, induces cellular proliferation and dysplasia by toll-like receptor (TLR) 2– and TLR4-dependent increase in oxidative stress and cholesterol biosynthesis.

Potential bacterial underpinning of cancer was first highlighted by the role of Helicobacter pylori in gastric cancer. The advent of next-generation sequencing has expanded our reach, allowing interrogation into the role of unculturable organisms in development of cancer. Recent studies have identified Fusobacterium and Porphyromonas to be enriched in patients with colon cancer in the United States. The current study found Peptostreptococcus anaerobius correlated with progression to colon cancer in a Chinese population. They further confirmed that P. anaerobius was also enriched in colon cancer samples from four western countries.

In this study, the authors identified the mechanism by which P. anaerobius promotes cancer using the potent carcinogen azoxymethane (AOM) mouse model of colon cancer. They found that mice treated with antibiotics and exposed to AOM and P anaerobius had a significantly higher incidence of dysplasia than mice that did not receive P. anaerobius. To determine the specific pathways involved in development of dysplasia, they used cell lines in vitro and validated their findings in the mouse model. The authors found P. anaerobius increases reactive oxygen species (ROS) and cholesterol biosynthesis in a Toll-like receptor 2 (TLR2)– and TLR4-dependent manner, and the increased intracellular cholesterol in turn enhances cellular proliferation.

This study provides novel mechanistic insight into the role of P. anaerobius in colon cancer. The identification of P. anaerobius in multiple patient cohorts further increases its relevance as a therapeutic target for colon cancer across the globe. The identification of the specific pathway driven by the bacteria provides both microbial and host targets for development of targeted therapies in colon cancer. Future prospectively conducted longitudinal studies in patients before they develop colon cancer can help further validate the relevance of these findings in human subjects.

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