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

Authors

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

Date of this Version

4-2020

Citation

Published in Gastroenterology 158:5 (April 2020), pp 1313–1325.

doi 10.1053/j.gastro.2019.12.029

Comments

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

Abstract

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.