Fat, fibre and cancer risk in African Americans and rural Africans

Abstract

Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (<5:100,000). The higher rates are associated with higher animal protein and fat and lower fiber consumption, higher colonic secondary bile acids, lower colonic short chain fatty acid quantities and higher mucosal proliferative biomarkers of cancer risk in otherwise healthy middle aged volunteers. Here we investigate further the role of fat and fiber in this association. We performed two-week food exchanges in subjects from the same populations, where African Americans were fed a high-fiber, lowfat African-style diet, and rural Africans a high-fat low-fiber western-style diet under close supervision. In comparison to their usual diets, the food changes resulted in remarkable reciprocal changes in mucosal biomarkers of cancer risk and in aspects of the microbiota and metabolome known to affect cancer risk, best illustrated by increased saccharolytic fermentation and butyrogenesis and suppressed secondary bile acid synthesis in the African Americans.

Taurocholic acid metabolism by gut microbes and colon cancer

“…47 A recent 2-week food exchange study between NA and AA (NA consumed animal-based diet, AA consumed vegetarian-based diet) demonstrate rapid reciprocal changes in levels of bacteria responsible for sulfide production (B. wadsworthia, Desulfovibrio spp) and protective butyrate production, as well as levels of DCA producing bacteria (C. scindens) and DCA in stool. 48 These results confirm a recent short-term diet exchange focusing on animal-and plant-based diets which found enhanced DCA formation and increased levels of taurine-utilizing, sulfide-producing B. wadsworthia. 47 AA were dominated by Bacteroides while NA by Prevotella consistent with the study by David et al (2013).…”

“…39 Evidence is emerging that as animal-based diets stimulate more bile input into the gut the levels of DCA-producing bacteria increase. 47,48 LCA is also produced from the 7a-dehydroxylation of CDCA or the 7b-dehydroxylation of UDCA and is highly toxic (potentially genotoxic and tumor-promoting). However, LCA does not tend to accumulate in the bile acid pool because it is efficiently excreted in feces by 2 mechanisms: 1) Being monohydroxylated, it is insoluble in fecal water and efficiently precipitates out in the acidic pH of the colon particularly in the presence of Ca 2C ions; and 2) binding of LCA to VDR results in enzymatic sulfation of LCA 49 whose hydrophilicity prevents passive absorption in colonocytes and allows removal from the body.…”

“…14 Similarly, the NA population was found to have significantly lower fecal total bile acids and significantly lower fecal DCA than AA consistent with lower meat intake. 48,78 The role of DCA as a tumor promoter was established in animal models during this period. Singledose intrarectal infusions of the carcinogen N-methyl-N 0 nitro-N-nitrosoguanidine (MNNG) followed by repeated rectal infusion doses of DCA significantly induced colorectal neoplasms, while DCA infusion alone was insufficient to induce tumor formation in both germ-free and conventional rats.…”

“…47,48 David et al (2013) exchanged a plant-based and animal-based diet in healthy American volunteers and measured gut microbiome and key metabolites, including SCFA and bile acids. 47 They showed that Prevotella, the major bacterial genus in NA, was reduced in subjects consuming an animal-based diet.…”

“…47 NA had higher abundance of starch degrading gut bacteria (diet high in resistant starch), carbohydrate fermenters and butyrate producers and metabolites, while Americans had higher levels of potentially pathogenic proteobacteria (Escherichia and Acinetobacter) and bile acid deconjugators and their metabolic end products. 48,78 O'Keefe et al (2015) also measured colonic inflammation and found that it went below NA baseline when AA were placed on NA diet, while NA colonic inflammation went above AA baseline when NA were placed on AA diet. 48 Butyrate production was associated with lower mucosal proliferation both in NA consuming high-fiber diet and AA switched to NA diet.…”