Association Between Sulfur-Metabolizing Bacterial Communities in Stool and Risk of Distal Colorectal Cancer in Men

  • Long H. Nguyen
    Affiliations
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • Wenjie Ma
    Affiliations
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
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  • Dong D. Wang
    Affiliations
    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

    Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • Yin Cao
    Affiliations
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, Missouri

    Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri
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  • Himel Mallick
    Affiliations
    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

    Broad Institute of MIT and Harvard, Cambridge, Massachusetts
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  • Teklu K. Gerbaba
    Affiliations
    Department of Food Science & Technology, University of Nebraska, Lincoln, Nebraska
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  • Jason Lloyd-Price
    Affiliations
    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

    Broad Institute of MIT and Harvard, Cambridge, Massachusetts
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  • Galeb Abu-Ali
    Affiliations
    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • A. Brantley Hall
    Affiliations
    Broad Institute of MIT and Harvard, Cambridge, Massachusetts
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  • Daniel Sikavi
    Affiliations
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
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  • David A. Drew
    Affiliations
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • Raaj S. Mehta
    Affiliations
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
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  • Cesar Arze
    Affiliations
    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • Amit D. Joshi
    Affiliations
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
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  • Yan Yan
    Affiliations
    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • Tobyn Branck
    Affiliations
    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • Casey DuLong
    Affiliations
    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • Kerry L. Ivey
    Affiliations
    Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

    South Australian Health and Medical Research Institute, Microbiome & Host Health Programme, Precision Medicine Theme, South Australia, Australia
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  • Shuji Ogino
    Affiliations
    Broad Institute of MIT and Harvard, Cambridge, Massachusetts

    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

    Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, Massachusetts

    Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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  • Eric B. Rimm
    Affiliations
    Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • Mingyang Song
    Affiliations
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • Wendy S. Garrett
    Affiliations
    Broad Institute of MIT and Harvard, Cambridge, Massachusetts

    Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts

    Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • Jacques Izard
    Affiliations
    Department of Food Science & Technology, University of Nebraska, Lincoln, Nebraska

    Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska
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  • Author Footnotes
    § Authors share co-senior authorship.
    Curtis Huttenhower
    Correspondence
    Curtis Huttenhower, PhD, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Associate Member, Broad Institute of MIT and Harvard, 677 Huntington Avenue, Boston, Massachusetts 02115.
    Footnotes
    § Authors share co-senior authorship.
    Affiliations
    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

    Broad Institute of MIT and Harvard, Cambridge, Massachusetts
    Search for articles by this author
  • Author Footnotes
    § Authors share co-senior authorship.
    Andrew T. Chan
    Correspondence
    Correspondence Address correspondence to: Andrew T. Chan, MD, MPH, Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, GRJ-825C, Boston, Massachusetts 02114.
    Footnotes
    § Authors share co-senior authorship.
    Affiliations
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

    Broad Institute of MIT and Harvard, Cambridge, Massachusetts

    Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
    Search for articles by this author
  • Author Footnotes
    § Authors share co-senior authorship.
Published:January 20, 2020DOI:https://doi.org/10.1053/j.gastro.2019.12.029

      Background & Aims

      Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide (H2S), have been associated with development of colorectal cancer (CRC). We identified a dietary pattern associated with sulfur-metabolizing bacteria in stool and then investigated its association with risk of incident CRC using data from a large prospective study of men.

      Methods

      We collected data from 51,529 men enrolled in the Health Professionals Follow-up Study since 1986 to determine the association between sulfur-metabolizing bacteria in stool and risk of CRC over 26 years of follow-up. First, in a subcohort of 307 healthy men, we profiled serial stool metagenomes and metatranscriptomes and assessed diet using semiquantitative food frequency questionnaires to identify food groups associated with 43 bacterial species involved in sulfur metabolism. We used these data to develop a sulfur microbial dietary score. We then used Cox proportional hazards modeling to evaluate adherence to this pattern among eligible individuals (n = 48,246) from 1986 through 2012 with risk for incident CRC.

      Results

      Foods associated with higher sulfur microbial diet scores included increased consumption of processed meats and low-calorie drinks and lower consumption of vegetables and legumes. Increased sulfur microbial diet scores were associated with risk of distal colon and rectal cancers, after adjusting for other risk factors (multivariable relative risk, highest vs lowest quartile, 1.43; 95% confidence interval 1.14–1.81; P-trend = .002). In contrast, sulfur microbial diet scores were not associated with risk of proximal colon cancer (multivariable relative risk 0.86; 95% CI 0.65–1.14; P-trend = .31).

      Conclusions

      In an analysis of participants in the Health Professionals Follow-up Study, we found that long-term adherence to a dietary pattern associated with sulfur-metabolizing bacteria in stool was associated with an increased risk of distal CRC. Further studies are needed to determine how sulfur-metabolizing bacteria might contribute to CRC pathogenesis.

      Keywords

      Abbreviations used in this article:

      BMI (body mass index), CRC (colorectal cancer), EC (Enzyme Commission), FFQ (food frequency questionnaire), GI (gastrointestinal), H2S (hydrogen sulfide), HPFS (Health Professionals Follow-up Study), IBD (inflammatory bowel disease), MLVS (Men’s Lifestyle Validation Study)
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