Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer

Abstract

Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal cancer (CRC). However, it is unclear whether changes in the intestinal microbiome contribute to the development of sporadic CRC or result from it. Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC. Factors that affect risk of CRC also affect the intestinal microbiome, including overweight and obesity; physical activity; and dietary intake of fiber, whole grains, and red and processed meat. These factors alter microbiome structure and function, along with the metabolic and immune pathways that mediate CRC development. We review epidemiologic and laboratory evidence for the influence of the microbiome, diet, and environmental factors on CRC incidence and outcomes. Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment. Integrated prospective studies are urgently needed to investigate these strategies.

Keywords: Colitis; Dysbiosis; Fecal Microbiota Transplant; Infection.

Figure 1.

Pathways by which dietary and environmental factors affect the intestinal microbiome and their roles in colorectal carcinogenesis. Obesity may promote CRC through LPS-mediated systemic inflammation and depletion of A muciniphila and SCFA-producing bacteria, whereas physical activity might protect against CRC by increasing the abundance of A muciniphila and SCFA-producing bacteria. The benefit of dietary fiber might be mediated by enrichment of SCFA-producing bacteria and increased production of SCFAs that inhibit CRC development, modulation of the immune and metabolic response. Red and processed meat may increase CRC risk by increased bacterial production of secondary bile acids, H₂S, and TMAO. Abbreviations: H₂S, hydrogen sulfide; T-reg cell, T-regulatory cells.