Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans

Abstract

Background: Epidemiologic studies have suggested that most cases of sporadic colon cancer can be attributed to diet. The recognition that colonic microbiota have a major influence on colonic health suggests that they might mediate colonic carcinogenesis. Objective: To examine the hypothesis that the influence of diet on colon cancer risk is mediated by the microbiota through their metabolites, we measured differences in colonic microbes and their metabolites in African Americans with a high risk and in rural native Africans with a low risk of colon cancer. Design: Fresh fecal samples were collected from 12 healthy African Americans aged 50-65 y and from 12 age-and sex-matched native Africans. Microbiomes were analyzed with 16S ribosomal RNA gene pyrosequencing together with quantitative polymerase chain reaction of the major fermentative, butyrate-producing, and bile acid-deconjugating bacteria. Fecal short-chain fatty acids were measured by gas chromatography and bile acids by liquid chromatography-mass spectrometry. Results: Microbial composition was fundamentally different, with a predominance of Prevotella in native Africans (enterotype 2) and of Bacteroides in African Americans (enterotype 1). Total bacteria and major butyrate-producing groups were significantly more abundant in fecal samples from native Africans. Microbial genes encoding for secondary bile acid production were more abundant in African Americans, whereas those encoding for methanogenesis and hydrogen sulfide production were higher in native Africans. Fecal secondary bile acid concentrations were higher in African Americans, whereas short-chain fatty acids were higher in native Africans. Conclusion: Our results support the hypothesis that colon cancer risk is influenced by the balance between microbial production of health-promoting metabolites such as butyrate and potentially carcinogenic metabolites such as secondary bile acids.Am J Clin Nutr 2013;98:111-20.

Taurocholic acid metabolism by gut microbes and colon cancer

“…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.…”

“…Prior studies by the same group showed that significantly higher levels of total fecal bile acids in AA than NA, and DCA in particular was significantly correlated (r 2 D0.65; PD0.01) with baiCD gene abundance-a gene in the bile acid-inducible operon of bile acid 7a-dehydroxylating bacteria such as Clostridium scindens and related organisms responsible for DCA production. 78 In summary, we propose a novel mechanism to explain why consumption of a high red meat and saturated fat diet imparts risk for CRC development involving primary microbial risk factors (bile acid metabolizing and sulfidogenic bacteria) that are modifiable by diet (Fig. 3).…”

“…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.…”

The Effects of Diet and the Microbiome on Reproduction and Longevity: A Comparative Review Across 5 Continents

“…A study of Native Africans and African Americans not only showed the genus Prevotella was higher in the former and Bacteroides more prevalent in the latter, but also showed higher diversity in the Americans supposedly because of a more diversified diet [59]. Although this study did not imply a more diverse microbiota is 'preferable' in terms of health, others have certainly implied this through association [60][61][62].…”

Chemopreventive Potential of Probiotics and Prebiotics

“…Butyrate is preferred by colonic cells over circulatory glucose or glutamine, to obtain up to a 70% of energy needs. Butyrate is an important tumor suppressant molecule formed during fermentation and exerts selective functions in normal and tumor colon cells [24]- [26]. It promotes growth in normal cells, while inhibiting growth in colon tumor cells by promoting apoptosis and suppressing proliferation.…”