An Empirical Dietary Pattern Associated with the Gut Microbial Features in Relation to Colorectal Cancer Risk.

BACKGROUND & AIMS: Epidemiologic evidence for dietary influence on colorectal cancer (CRC) risk through the gut microbiome remains limited.METHODS: Leveraging 307 men and 212 women with stool metagenomes and dietary data, we characterized and validated a sex-specific dietary pattern associated with the CRC-related gut microbial signature (CRC Microbial Dietary Score [CMDS]). We evaluated the associations of CMDS with CRC risk according to Fusobacterium nucleatum, pksEscherichia coli, and enterotoxigenic Bacteroides fragilis (ETBF) status in tumor tissue using Cox proportional hazards regression in the Health Professionals Follow-up Study (1986-2018), Nurses' Health Study (NHS) (1984-2020), and NHS II (1991-2019).RESULTS: The CMDS was characterized by high industrially processed foods and low unprocessed fiber-rich foods intakes. In 259,200 participants, we documented 3,854 incident CRC cases over 6,467,378 person-years of follow-up. CMDS was associated with a higher risk of CRC (P<0.001), with a multivariable hazard ratio (HR) of 1.25 (95%CI, 1.13-1.39). The association remained after adjusting for previously established dietary patterns, e.g., the Western and prudent diets. Notably, the association was stronger for tumoral F. nucleatum-positive (HR, 2.51; 95%CI, 1.68-3.75; P<0.001) (P=0.03, positivity vs. negativity), pksE. coli-positive (HR, 1.68; 95%CI, 0.84-3.38; P=0.005) (P=0.01, positivity vs. negativity), and ETBF-positive CRC (HR, 2.06; 95%CI, 1.10-3.88; P=0.016) (P=0.06, positivity vs. negativity), compared with their negative counterparts.CONCLUSIONS: CMDS was associated with increased CRC risk, especially for tumors with detectable F. nucleatum, pksE. coli, and ETBF in tissue. Our findings support a potential role of the gut microbiome underlying the dietary effects on CRC.