The Role of the Gut Microbiome in Colorectal Cancer
Abstract
Colorectal cancer is one of the most common types of cancer in active duty military personnel. Inflammatory bowel disease (IBD) is a chronic condition that predisposes individuals to develop colorectal cancer. The risk for a patient living with IBD is two times higher compared to the general population. The most recent statistics show that the prevalence of IBD has increased two- to three-fold among Veterans, suggesting that the threat of colorectal cancer in the military population is as real as in the civilian population. Chronic inflammation is one of the key hallmarks of cancer, and alteration to the structure of microbial communities (the microbiome) in the colon is considered a driver of tumor development. Certain bacterial populations are enriched in patients with IBD and colorectal cancer while suppressing others with potential antitumor effects. Our study is of high significance because our goal is to identify specific bacteria and bacterial products that are protective against intestinal inflammation and cancer. In this proposal, we meet the Peer Reviewed Cancer Research Program Idea Award with Special Focus on colorectal cancer overarching goals: (1) To identify genetics factors that play a role in shaping the composition of the intestinal microbiome with the intent to (2) identify specific microbial communities and bacterial products that can lower the incidence of IBD and colorectal cancer and thereby reduce the mortality associated with metastatic disease in active duty Service members, Veterans, and their families. The experiments described in this application will employ an established animal model of human IBD together with a different animal model that is less vulnerable to developing colorectal cancer in conditions of chronic intestinal inflammation. The experimental plan outlined in this application is structured around two focused specific aims. In the first aim, studies will be conducted to evaluate changes in the composition of microbial communities in the gut that are associated with reduced intestinal inflammation. We will determine their identities, production of bacterial products, and their capacity to reduce inflammation. Experiments under Aim 2 are designed to next examine IBD progression to colorectal cancer in early, middle, and late onset of disease by employing the same animal models as described in Aim 1. We will determine if there is a preferential expansion of specific microbial communities that are linked to reduced inflammation, delayed or tumor development that we will define as having healthy benefits. We then will test the anticancer activities of the specific bacterial species in our animal models of colorectal cancer. Completion of this project offers great promise in translating our observations to the clinic in the current era of probiotic medicine. Presently, beneficial live microorganisms termed probiotics are becoming increasingly part of our daily diets. We believe that our study has the potential to identify beneficial bacteria with anticancer effects. Our findings are expected to serve as a platform for formulating novel probiotics and compounds that are safe and cost effective for the treatment of early and advanced colorectal cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810240
Entities
People
- Ana Gamero
Organizations
- Temple University
- United States Army