Colon cancer is an environmental disease associated with westernization, and it has been shown that it takes one generation for immigrants to change their risk of cancer. To investigate the role of the western diet in driving this change, we have switched the macronutrient composition of diets of groups of 20 healthy middle aged African Americans, who have the highest risk of colon cancer in the USA (~65:100,000) and rural Africans, who rarely get the disease (<5:100,000) and measured its impact on mucosal biomarkers of cancer risk and the colonic microbiota that we hypothesize regulate this risk. Twenty healthy middle-aged volunteers from each community were housed for two weeks so that food could be prepared and consumed under close supervision. Americans were given a “traditional African” diet, high in fiber and low in meat and fat, while Africans were given a western diet, high in meat and fat, low in fiber. Mucosal biopsies taken from the proximal, mid and distal colon at colonoscopy before and after the dietary switch showed significant suppression of inflammation and proliferation cancer biomarkers in Americans and increases in Africans. In keeping with our hypothesis, these changes were associated with changes in bacterial co-occurrences, notably those of butyrate producers, and their metabolomic phenotypes. Targeted analysis of microbes associated with saccharolytic fermentation and their products, short chain fatty acids, showed that they were strongly associated with suppression of cancer biomarkers, whilst microbes associated with bile acid deconjugation and secondary bile acid production exhibited the reverse, providing a mechanism for the strong epidemiological evidence that fiber reduces risk and fat, by increasing the hepatic synthesis of bile acids, increases risk. In conclusion, our results build on the observation that the incidence of colon cancer changes within one generation of westernization by showing that the mucosal changes associated with carcinogenesis change within two weeks of switching to a western diet and provide evidence that the change is mediated by colonic microbial metabolism.

Citation Format: Stephen J. O'Keefe. Changes in diet and microbiome that mitigate CRC risk in Native Africans vs. African Americans. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA26.