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

Authors

Long H. Nguyen, Massachusetts General Hospital
Wenjie Ma, Massachusetts General Hospital
Dong D. Wang, Harvard University
Yin Cao, Massachusetts General Hospital
Himel Mallick, Harvard University
Teklu K. Gerbaba, University of Nebraska-Lincoln
Jason Lloyd-Price, Harvard University
Galeb Abu-Ali, Harvard University
A. Brantley Hall, Broad Institute of the Massachusetts Institute of Technology and Harvard University
Daniel Sikavi, Massachusetts General Hospital
David A. Drew, Massachusetts General Hospital
Raaj S. Mehta, Massachusetts General Hospital
Cesar Arze, Harvard University
Amit D. Joshi, Massachusetts General Hospital
Yan Yan, Harvard University
Tobyn Branck, Harvard University
Casey DuLong, Harvard University
Kerry L. Ivey, Harvard University
Shuji Ogino, Broad Institute of the Massachusetts Institute of Technology and Harvard University
Eric B. Rimm, Harvard University
Mingyang Song, Massachusetts General Hospital
Wendy S. Garrett, Broad Institute of the Massachusetts Institute of Technology and Harvard University
Jacques Izard, University of Nebraska-LincolnFollow
Cutis Huttenhower, Harvard UniversityFollow
Andrew T. Chan, Massachusetts General HospitalFollow

ORCID IDs

Izard https://orcid.org/0000-0002-5904-5436

Document Type

Article

Date of this Version

4-2020

Citation

Gastroenterology (April 2020) 158(5): 1,313–1,325

doi: 10.1053/j.gastro.2019.12.029

Comments

Copyright © 2020, AGA Institute; published by Elsevier. Used by permission

Abstract

Background and 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.