Does the tumor microbiome play a role in early-onset colorectal cancer?
Posted in News
BY BENJAMIN WEINBERG, MD
The human body is composed of around a trillion cells, and there are a trillion to a trillion-and-a-half bacterial cells composing our gut microbiome. Of these bacteria, some are good and help us digest foods. Others can behave badly and are associated with diseases such as autoimmunity and cancer. Bizarrely, the presence or absence of certain gut bacteria can lead patients to respond differently to certain medications. This finding has been demonstrated in patients with melanoma skin cancer undergoing immunotherapy: those patients with “good” gut bacteria had more tumor shrinkage compared to patients with “bad” gut bacteria, even though they were given the same drug! The specific bacteria may not matter as much as long as there is diversity within the microbiome – the more types of bacteria present, the better.
The field of microbiome research has exploded exponentially in recent years. The gut microbiome exists as an interplay between the environment (what we eat), our immune system, and our inherited susceptibility to disease (genetics).
All of these factors are independently associated with development of cancer; therefore, the microbiome is a potential target both to prevent cancers and to treat them once they occur.
In this vein, the findings by Riquelme and colleagues (1) are especially eye-opening. The investigators looked at the bacteria that reside within pancreatic tumors and compared bacterial and immune profiles from patients who lived more than 5 years following surgery to those who lived less than 5 years. The long-term survivors had a higher diversity of bacteria, a specific bacterial profile, and higher levels of immune cells within the tumor. Moreover, when they transplanted stool from long- vs. short-term pancreatic cancer survivors into mice with pancreatic tumors, the investigators could induce similar changes in the bacteria and the level of immune cells of mouse pancreatic tumors. This proof-of-principle could serve as the basis for future therapies designed to retrain the body’s immune system to fight pancreatic cancer.
Our own research (2) explores the differences in tumor microbiome in young- versus older-onset colorectal cancer. There has been a dramatic rise in individuals under the age of 50 developing colorectal cancer in the last 20 years, and no one has demonstrated a clear cause for this trend. Hypotheses include processed foods and the coincident epidemics of diabetes and obesity, but these alone are not enough to account for the increase in young-onset colorectal cancer. Thus, we are collecting tumor samples from patients with colorectal cancer diagnosed before age 45 and after age 65 and comparing their bacterial DNA. Our hope is that this research will find specific bacteria that play a causative role in young-onset colorectal cancer. Some bacteria that coexist with tumors may be passengers, just along for the ride, while others may be vital drivers promoting cancer growth. We need to figure out who is who, unlocking new doors to prevent and treat gastrointestinal cancers. These findings could alter how we screen for colorectal cancer in younger individuals by establishing a high-risk microbiome. They could also offer novel therapeutic options including antibiotics, probiotics, and vaccines to target the bacterial chaperones and slow down cancer growth.
1 Riquelme E, Zhang Y, Zhang L, et
al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell 178(4):795-806, 2019. https://www.pancan.org/news/bacteria-may-impact-pancreatic-cancer-survival/
2.Research is funded by the Colorectal Cancer Alliance’s Chris4Life Research Grant in Young Onset Colorectal Cancer and the Victoria Casey and Peter Teeley Foundation.
This article was published in the Fall 2019 Ruesch Newsletter. Read more from this issue here.