A prospective cohort analysis of gut microbial co-metabolism in Alaska Native and rural African people at high and low risk of colorectal cancer

Soeren Ocvirk, Annette S. Wilson, Joram M. Posma, Jia V. Li, Kathryn R. Koller, Gretchen M. Day, Christie A. Flanagan, Jill Evon Otto, Pam E. Sacco, Frank D. Sacco, Flora R. Sapp, Amy S. Wilson, Keith Newton, Faye Brouard, James P. Delany, Marissa Behnning, Corynn N. Appolonia, Devavrata Soni, Faheem Bhatti, Barbara MethéAdam Fitch, Alison Morris, H. Rex Gaskins, James Kinross, Jeremy K. Nicholson, Timothy K. Thomas, Stephen J.D. O'Keefe

Research output: Contribution to journalArticlepeer-review


Background: Alaska Native (AN) people have the world's highest recorded incidence of sporadic colorectal cancer (CRC) (∼91:100,000), whereas rural African (RA) people have the lowest risk (<5:100,000). Previous data supported the hypothesis that diet affected CRC risk through its effects on the colonic microbiota that produce tumor-suppressive or-promoting metabolites. Objectives: We investigated whether differences in these metabolites may contribute to the high risk of CRC in AN people. Methods: A cross-sectional observational study assessed dietary intake from 32 AN and 21 RA healthy middle-aged volunteers before screening colonoscopy. Analysis of fecal microbiota composition by 16S ribosomal RNA gene sequencing and fecal/urinary metabolites by 1H-NMR spectroscopy was complemented with targeted quantification of fecal SCFAs, bile acids, and functional microbial genes. Results: Adenomatous polyps were detected in 16 of 32 AN participants, but not found in RA participants. The AN diet contained higher proportions of fat and animal protein and less fiber. AN fecal microbiota showed a compositional predominance of Blautia and Lachnoclostridium, higher microbial capacity for bile acid conversion, and low abundance of some species involved in saccharolytic fermentation (e.g., Prevotellaceae, Ruminococcaceae), but no significant lack of butyrogenic bacteria. Significantly lower concentrations of tumor-suppressive butyrate (22.5 ± 3.1 compared with 47.2 ± 7.3 SEM μmol/g) coincided with significantly higher concentrations of tumor-promoting deoxycholic acid (26.7 ± 4.2 compared with 11 ± 1.9 μmol/g) in AN fecal samples. AN participants had lower quantities of fecal/urinary metabolites than RA participants and metabolite profiles correlated with the abundance of distinct microbial genera in feces. The main microbial and metabolic CRC-associated markers were not significantly altered in AN participants with adenomatous polyps. Conclusions: The low-fiber, high-fat diet of AN people and exposure to carcinogens derived from diet or environment are associated with a tumor-promoting colonic milieu as reflected by the high rates of adenomatous polyps in AN participants.

Original languageEnglish (US)
Pages (from-to)406-419
Number of pages14
JournalAmerican Journal of Clinical Nutrition
Issue number2
StatePublished - Feb 1 2020


  • Alaska Native people
  • bile acids
  • butyrate
  • colorectal cancer
  • deoxycholic acid
  • dietary fiber
  • gut microbiota
  • rural African people
  • short-chain fatty acids

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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