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

Abstract

Epidemiologic evidence for dietary influence on colorectal cancer (CRC) risk through the gut microbiome remains limited. 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, pks⁺Escherichia coli, and enterotoxigenic Bacteroides fragilis status in tumor tissue using Cox proportional hazards regression in the Health Professionals Follow-Up Study (1986-2018), Nurses' Health Study (1984-2020), and Nurses' Health Study II (1991-2019). The CMDS was characterized by high industrially processed food and low unprocessed fiber-rich food intakes. In 259,200 participants, we documented 3854 incident CRC cases over 6,467,378 person-years of follow-up. CMDS was associated with a higher risk of CRC (P_trend < .001), with a multivariable hazard ratio (HR_{Q5 vs Q1}) of 1.25 (95% CI, 1.13-1.39). The association remained after adjusting for previously established dietary patterns, for example, the Western and prudent diets. Notably, the association was stronger for tumoral F nucleatum-positive (HR_{Q5 vs Q1}, 2.51; 95% CI, 1.68-3.75; P_trend < .001; P_{heterogeneity} = .03, positivity vs negativity), pks⁺E coli-positive (HR_{Q5 vs Q1}, 1.68; 95% CI, 0.84-3.38; P_trend = .005; P_{heterogeneity} = .01, positivity vs negativity), and enterotoxigenic Bacteroides fragilis-positive CRC (HR_{Q5 vs Q1}, 2.06; 95% CI, 1.10-3.88; P_trend = .016; P_{heterogeneity} = .06, positivity vs negativity), compared with their negative counterparts. CMDS was associated with increased CRC risk, especially for tumors with detectable F nucleatum, pks⁺E coli, and enterotoxigenic Bacteroides fragilis in tissue. Our findings support a potential role of the gut microbiome underlying the dietary effects on CRC.