Diet, Microbiota, and Microbial Metabolites in Rural Africans and African Americans

Abstract

Epidemiological studies have provided strong evidence that sporadic colon cancer risk is driven by diet, with red meat and fat increasing, and fibre suppressing risk 1,2 and yet human dietary intervention studies with low fat, high fibre diets have yielded disappointing results 3. To investigate this controversy, we performed strictly controlled in‐house studies where the diets of high risk African Americans (high meat and fat, low fibre) and low risk rural Africans (low meat and fat, high fibre) were switched for two weeks, and at the same time interrogated the hypothesis that diet mediates cancer risk through its effects on microbiota metabolism. Diet switch induced significant reciprocal changes in mucosal biomarkers of inflammation and cancer risk, with reductions in African Americans and increases in Africans. That these changes were mediated by the microbiota was evidenced by similar reciprocal changes in its composition and function, exemplified by a loosening of the robust interaction structure geared to complex plant carbohydrate degradation and butyrate production in Africans, and a strengthening of intermicrobial connectivity in African Americans. Furthermore, phenotypic shifts in the metabolome revealed potential mechanisms responsible for the mucosa changes, with increased saccharolytic fermentation and anti‐neoplastic butyrate production and reduced microbial generation of pro‐carcinogenic secondary bile acids in Americans, and the reverse in Africans. In conclusion, our study reveals mechanisms responsible for the epidemiological association between western diets and high colon cancer risk, and indicates that halving fat intake and increasing fibre intake to approximately 50g/d (i.e. far greater changes than those achieved by past intervention studies) can be expected to have an immediate effect on cancer risk. Our findings also warn against the progressive westernization of the traditional African diet, where a reduction in butyrogenesis may permit the progression of chronic inflammation to neoplasia.