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

Long H Nguyen, Wenjie Ma, Dong D Wang, Yin Cao, Himel Mallick, Teklu K Gerbaba, Jason Lloyd-Price, Galeb Abu-Ali, A Brantley Hall, Daniel Sikavi, David A Drew, Raaj S Mehta, Cesar Arze, Amit D Joshi, Yan Yan, Tobyn Branck, Casey DuLong, Kerry L Ivey, Shuji Ogino, Eric B RimmMingyang Song, Wendy S Garrett, Jacques Izard, Curtis Huttenhower, Andrew T Chan

Research output: Contribution to journalArticle

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 meta-transcriptomes and assessed diet using semi-quantitative 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% CI, 1.14-1.81; Ptrend=.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; Ptrend=.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.

Original languageEnglish
JournalGastroenterology
DOIs
Publication statusE-pub ahead of print - 20 Jan 2020

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