Geographical and migration epidemiological studies, backed up by experimental studies, have produced overwhelming evidence that diet drives colon cancer risk, with high intakes of meat and fat increasing risk, and high consumption rates of fiber rich foods, such as grains, fruits and vegetables, reducing risk. To test our hypothesis that cancer risk is determined by the effect the diet has on the composition and function of the microbiota to produce metabolites that either promote mucosal health or are inflammatory and neoplastic, we have conducted studies in populations of high and low risk, namely African Americans who have the highest risk in the USA, and rural Africans, who rarely get the disease, and confirmed that high meat and fat intakes in Americans were associated with increased mucosal proliferation rates - a biomarker of cancer risk, while high fibre African diets were associated with low proliferation rates. Simultaneous measurement of the microbiota and metabolome showed dramatic differences in the microbiota composition and function. The structure of the African colonic microbiota was considerably more robust, with amplification of the bacterial groups associated with complex plant carbohydrate degradation and butyrate production. Targeted analysis confirmed higher numbers of butyrate-producing bacteria and butyrate, which has profound anti-neoplastic properties in experimental models. In contrast, secondary bile acid producing bacteria and their products, which have carcinogenic properties, were higher in African Americans. Most recently, we have demonstrated that dietary switch between these two populations produces reciprocal changes in the microbiome, metabolome, and mucosal biomarkers of risk within 2 weeks, leading to the conclusion that modification of the diets of westernized populations to contain high fiber (>45g/d) foods, such as grains and beans, together with lower intakes of animal fats, can be expected to have an immediate effect on cancer risk.