The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors

Authors

Long H. Nguyen, Massachusetts General Hospital
Yin Cao, Washington University School of Medicine in St. Louis
Jinhee Hur, Harvard University
Raaj S. Mehta, Massachusetts General Hospital
Daniel R. Sikavi, Massachusetts General Hospital
Yiqing Wang, Massachusetts General Hospital
Wenjie Ma, Massachusetts General Hospital
Kana Wu, Harvard University
Mingyang Song, Massachusetts General Hospital
Edward L. Giovannucci, Harvard University
Eric B. Rimm, Harvard University
Walter C. Willett, Harvard University
Wendy S. Garrett, Broad Institute of the Massachusetts Institute of Technology and Harvard University
Jacques Izard, University of Nebraska-LincolnFollow
Curtis Huttenhower, Harvard UniversityFollow
Andrew T. Chan, Massachusetts General HospitalFollow

Author ORCID Identifier

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

Date of this Version

11-2021

Document Type

Article

Citation

Gastroenterology (November 2021) 161(5): 1,423–1,432

doi: 10.1053/j.gastro.2021.07.008.e4

HHS public access author manuscript, PMC 8545755

Comments

Copyright © 2021, AGA Institute; Elsevier. Used by permission

Abstract

Background and aims: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H₂S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking.

Methods: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses’ Health Study II (1991–2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: We documented 2,911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (ORquartile [Q]4 versus Q1, 1.31; 95% CI, 1.10–1.56, Ptrend = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (ORQ4 versus Q1, 1.65 for villous/tubulovillous histology; 95% CI, 1.12–2.43; Ptrend = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50.

Conclusions: Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.

Includes supplemental materials.