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 fibre 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 fibre in this association. We performed 2-week food exchanges in subjects from the same populations, where African Americans were fed a high-fibre, low-fat African-style diet and rural Africans a high-fat, low-fibre western-style diet, under close supervision. In comparison with 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.

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We thank Chadd and Kate Bain, and the iZulu Lodge and Projects team in KwaZulu-Natal, for help with the recruitment and housing of the African volunteers, and Dr Iain Thirsk and his surgical endoscopy staff at Ngwelezana Hospital, Empangeni, KwaZulu-Natal, for providing the endoscopic facilities for the study, and Faye Brouard for help with the rural dietary assessments. We acknowledge the help of Dr Robert Branch and the staff of the University of Pittsburgh Clinical Translation and Research Center for help with the dietary switch studies on African Americans. We thank Ms Kayellen Umeakunne for help with the design of the intervention diets. Primary funding for the study was provided by a grant from the National Institutes of Health R01 CA135379 (O’Keefe) and CTRC support from UL1 RR024153 and UL1TR000005. The research was also supported by the National Institute for Health Research Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. We acknowledge the Academy of Medical Sciences, which funded part of the metabolic profiling work. Additional funding for the microbiota studies was provided by the Spinoza Award of the Netherlands Organization (de Vos) for Scientific Research, the ERC Advanced Grant 250172 (Microbes Inside) of the European Research Council and the Academy of Finland (grant 141140 to W.M.dV. and grant 256950 to L.L.). The University of Pittsburgh Genomics and Proteomics Core Laboratory (GPCL) produced the mucosal gene expression microarray data.

Author information

Author notes

    • Franck Carbonero

    Present address: Department of Food Science, University of Arkansas, Fayetteville, Arizona 72704, USA


  1. Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA

    • Stephen J. D. O’Keefe
    • , Junhai Ou
    • , Khaled Mohammed
    • , Elaine Wahl
    • , Kishore Vipperla
    •  & Hatem O. Kaseb
  2. Department of Surgery and Cancer and Centre for Digestive and Gut Health, Institution of Global Health Innovation, Imperial College, London SW7 2AZ, UK

    • Jia V. Li
    • , Joram M. Posma
    • , James Kinross
    •  & Jeremy K. Nicholson
  3. Laboratory of Microbiology, Wageningen University, Wageningen 6703 HB, The Netherlands

    • Leo Lahti
    • , Sebastian Tims
    • , Philippe G. B. Puylaert
    • , Willem M. de Vos
    •  & Erwin G. Zoetendal
  4. Department of Veterinary Bioscience, University of Helsinki, Helsinki, Finland

    • Leo Lahti
    •  & Willem M. de Vos
  5. University of Illinois at Urbana–Champaign, Champaign, Illinois 61801, USA

    • Franck Carbonero
    • , Ann C. Benefiel
    •  & H. Rex Gaskins
  6. Division of Sports Medicine and Nutrition, School of Health and Rehabilitation Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA

    • Elizabeth Ruder
  7. University of KwaZulu-Natal, Durban, South Africa

    • Vasudevan Naidoo
    • , Lungile Mtshali
    •  & Keith Newton
  8. Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA

    • James DeLany
  9. Division of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA

    • Alyssa Krasinskas
  10. RPU Immunolbiology, Department of Bacteriology and Immunology, University of Helsinki, Helsinki 00014, Finland

    • Willem M. de Vos


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S.J.D.O’K. designed and conducted the human studies, supervised the analysis and evaluation the results, prepared, edited and revised the manuscript. E.G.Z. assisted with study design, managed the global microbiota analysis and interpretation, and assisted with preparation of the manuscript. H.R.G. assisted with study design and execution of the human studies, managed the targeted microbiota analysis and interpretation, and assisted with preparation of the manuscript. J.K. was responsible for writing the text relating to the 1H NMR analysis and for interpreting the spectral data. J.N. provided strategic oversight for the metabonomic analytical strategy and was responsible for data interpretation. J.L. performed the 1H NMR analysis and the multivariate analysis. J.O. was responsible for targeted analysis of metabolites, data management, sample distribution and manuscript preparation. L.L. and S.T. conducted the microbiota data analysis and interpretation, and assisted with preparation of the manuscript. P.P. sample coordination and microbiota phylogenetic profiling. W.M.D.V. managed, interpreted and supported microbiota analysis. K.M. and H.K. performed the mucosal immunohistochemistry. E.W. (USA), E.R. (USA) and F.B. (S Africa) performed the dietary analysis, meal design and production. K.A.N. and V.N. helped organize the South African studies and endoscopies. K.V. was responsible for the screening, recruitment and management of African Americans dietary switch studies. F.C. performed the targeted microbiota analysis. L.M. supervised the recruitment of African subjects and helped with the dietary exchange studies. A.K. supervised the histological assessments of biopsy samples. A.C.B. coordinated the targeted microbiota analyses. J.D. supervised the targeted metabolite analysis and helped with manuscript preparation. J.P. carried out the metabolic reaction network analysis and interpretation.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Stephen J. D. O’Keefe.

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    Supplementary Information

    Supplementary Figures 1-6, Supplementary Tables 1-11, Supplementary Discussion, Supplementary Methods, and Supplementary References


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