How the Microbiome Can Affect Cancer

Guest Post by William G. Nelson, MD, PhD
Editor-in-Chief, Cancer Today

Over the past few years, scientists have come to a deeper understanding of how microorganisms can cause chronic human diseases, based on the recognition that each human body contains at least 40 trillion microorganisms. This collection of microorganisms (or microbiota) populates complex ecosystems called microbiomes in the skin, nose, mouth, stomach, and intestines. Some 99 percent of the microbiota in the human body resides in the gastrointestinal microbiome, which is increasingly seen as a major determinant of health and disease—including cancer.

Photo by Joe Rubino

The mechanisms by which gut microorganisms contribute to cancer formation are just beginning to be understood. Cynthia Sears, an infectious disease specialist at Johns Hopkins now working on how intestinal bacteria may cause colorectal cancers, has identified one bug called Bacteroides fragilis as a particularly bad actor. This bacterium produces a toxin that damages normal intestinal cells, leading to a chronically inflamed intestinal microbiome prone to generate cancers. When Dr. Sears transferred the bacterium to mice inclined to develop benign intestinal polyps, the mice formed colorectal cancers instead.

In a paper published in April 2016 in Cancer Research, a journal of the American Association for Cancer Research, Dr. Sears and her colleagues reported that colorectal cancers associated with B. fragilis could be suppressed, not just by eradicating the microorganism, but also by reducing inflammation. This opens up new avenues for preventing colorectal cancers by altering the relationships between the microbiota and immune cells in the gut microbiome. Several other intestinal bacteria are also likely to affect colorectal cancer development. A gut microbiota rich in these pro-cancer bacteria may drive a microbiome toward chronic inflammation and cancer.

The influence of the intestinal microbiota on immune responses may even extend to how effectively the body’s immune system can be activated to fight cancers. Two recent reports in Science suggest that the presence of certain bacteria in the intestinal microbiome was accompanied by better anti-cancer responses to immunotherapy. The bacteria enhanced the effects of new immunotherapy drugs like Yervoy (ipilimumab), Opdivo (nivolumab), and Keytruda (pembrolizumab).

The study of the microbiome in the human intestine and at other sites is reaching a fever pitch. Hopefully, the future will bring answers to many questions being raised. Will altering the microbiota and microbiome be a cornerstone of cancer prevention and treatment? Can so-called probiotics be developed and demonstrated to improve health? What is a healthy microbiome and how can it be maintained? Finding answers to these questions may go a long way toward preventing and treating human cancers.

William G. Nelson, MD, PhD, is the editor-in-chief of Cancer Today, the quarterly magazine for cancer patients, survivors, and caregivers published by the American Association for Cancer Research. Nelson is the Marion I. Knott professor of oncology and director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore. You can read his complete column in the winter 2016/2017 issue of Cancer Today.

 

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