Diets that promote intestinal inflammation can increase risk of colorectal carcinomas associated with specific bacteria in the microbiome, researchers report in the October issue of Clinical Gastroenterology and Hepatology. Diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal cancer risk, which might be reduced with dietary changes.
Chronic inflammation of the intestine, a risk factor colorectal carcinoma, has been associated with specific diets and bacterial species in the intestinal microbiota. Intestinal inflammation decreases production of protective mucins and antimicrobial peptides, which could increase adherence of bacteria to the mucosa. Impaired mucosal barrier function allows bacteria to readily interact with the epithelium and colonize colonic mucosa. This increases exposure of intestinal cells to bacterial metabolites, which can be mutagenic.
Some gut microbiota, including Fusobacterium nucleatum, contribute to carcinogenesis by altering expression of transcription factors, oncogenes, and genes that regulate inflammation and recruitment of monocytes and myeloid-derived suppressor cells. The presence of F nucleatum in tumor tissues has been associated with proximal tumor location, serrated neoplasia, microsatellite instability (MSI), high numbers of macrophages, disease progression, and chemoresistance in patients with colorectal cancer.
Li Liu et al therefore investigated the association between diets that promote inflammation and colorectal tumors that contain F nucleatum.
They collected data from the Nurses’ Health Study and the Health Professionals Follow-up Study, analyzing information on dietary intake, incidence of colorectal cancer, and detection of F nucleatum in tumor tissues.
The inflammatory effects of diets were estimated based on the empirical dietary inflammatory pattern (EDIP) score—the sum of weighted intake scores of 18 foods (processed meat, red meat, organ meat, fish, vegetables other than green leafy vegetables and dark yellow vegetables, refined grains, high-energy beverages, low-energy beverages, tomatoes, beer, wine, tea, coffee, dark yellow vegetables, green leafy vegetables, snacks, fruit juice, and pizza). These food were selected based on their effects on plasma levels of interleukin 6, C-reactive protein, and tumor necrosis factor–receptor superfamily member 1B, (TNFRSF1B). Higher scores indicate inflammatory diets and lower scores indicate anti-inflammatory diets.
The subjects were categorized into tertiles using cohort-specific cut-off points of the cumulative average EDIP scores. Information on lifestyles and medication was assessed using biennial questionnaires in both cohorts as previously described
During 28 years of follow up, of 124,433 participants, Liu found 951 incident cases of colorectal carcinoma with tissue F nucleatum.
Liiu associated higher EDIP scores with increased risk of F nucleatum–positive colorectal tumors for subjects in the highest vs lowest EDIP score tertiles. The hazard ratio for F nucleatum–positive colorectal tumors was 1.63. EDIP scores did not associate with F nucleatum–negative tumors.
High EDIP scores associated with proximal F nucleatum–positive colorectal tumors but not with proximal F nucleatum–negative colorectal tumors. The association appeared to be generally consistent irrespective of tumor MSI or PTGS2 status.
The authors conclude that increasing our understanding of the interactions among diet, intestinal inflammation, the microbiota, and carcinogenesis might help us design strategies to prevent colorectal carcinoma.