Association Between the Sulfur Microbial Diet and Risk of Colorectal Cancer

Yiqing Wang,Raaj S Mehta,Long H Nguyen,Andrew T Chan,Mingyang Song,Curtis Huttenhower

doi:10.1001/jamanetworkopen.2021.34308

Yiqing Wang, Raaj S Mehta + Show 4 more

Open Access

https://doi.org/10.1001/jamanetworkopen.2021.34308

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Abstract

Sulfur-metabolizing bacteria that reduce dietary sulfur to hydrogen sulfide have been associated with colorectal cancer (CRC). However, there are limited studies investigating the association between diet and sulfur-metabolizing bacteria in the development of CRC. To develop a dietary score that correlates with gut sulfur-metabolizing bacteria and to examine its association with CRC risk. This prospective cohort study included data from the Health Professionals Follow-up Study (1986-2014), Nurses' Health Study (1984-2016), and Nurses' Health Study II (1991-2017). Participants were US male health professionals and female registered nurses who were free of inflammatory bowel disease and cancer at baseline, with a subsample of participants who provided stool samples from 2012 to 2014. Statistical analysis was conducted from September 1, 2020, to June 1, 2021. A dietary pattern, assessed by a food-frequency questionnaire, that most correlated with 43 sulfur-metabolizing bacteria identified through taxonomic and functional profiling of gut metagenome data. Incident CRC. Among 214 797 participants comprising 46 550 men (mean [SD] age at baseline, 54.3 [9.7] years) and 168 247 women (mean [SD] age at baseline, 43.0 [9.2] years), 3217 incident cases of CRC (1.5%) were documented during 5 278 048 person-years of follow-up. The sulfur microbial diet, developed in a subsample of 307 men (mean [SD] age, 70.5 [4.3] years) and 212 women (mean [SD] age, 61.0 [3.8] years), was characterized by high intakes of low-calorie beverages, french fries, red meats, and processed meats and low intakes of fruits, yellow vegetables, whole grains, legumes, leafy vegetables, and cruciferous vegetables. After adjustment for other risk factors, greater adherence to the sulfur microbial diet was associated with an increased risk of CRC, with a hazard ratio (HR) of 1.27 (95% CI, 1.12-1.44) comparing the highest vs the lowest quintile of the diet score (linear trend of diet score quintiles; P < .001 for trend). When assessed by anatomical subsites, greater adherence to the sulfur microbial diet was positively associated with distal CRC (HR, 1.25; 95% CI, 1.05-1.50; P = .02 for trend) but not proximal colon cancer (HR, 1.13; 95% CI, 0.93-1.39; P = .19 for trend). Adherence to the sulfur microbial diet was associated with an increased risk of CRC, suggesting a potential mediating role of sulfur-metabolizing bacteria in the associaton between diet and CRC. Further research is needed to confirm these findings and to determine the underlying mechanisms.

Highlights

Diet is an important modifiable risk factor for colorectal cancer (CRC), the third most common cancer worldwide and the second leading cause of cancer death according to GLOBOCAN 2020.1 the roles of specific gut microbial activities in the diet-CRC association have not been thoroughly investigated
After adjustment for other risk factors, greater adherence to the sulfur microbial diet was associated with an increased risk of CRC, with a hazard ratio (HR) of 1.27 comparing the highest vs the lowest quintile of the diet score
When assessed by anatomical subsites, greater adherence to the sulfur microbial diet was positively associated with distal CRC (HR, 1.25; 95% CI, 1.05-1.50; P = .02 for trend) but not proximal colon cancer (HR, 1.13; 95% CI, 0.93-1.39; P = .19 for trend)

Summary

Introduction

Diet is an important modifiable risk factor for colorectal cancer (CRC), the third most common cancer worldwide and the second leading cause of cancer death according to GLOBOCAN 2020.1 the roles of specific gut microbial activities in the diet-CRC association have not been thoroughly investigated. A recent study developed a de novo dietary score associated with the enrichment of sulfurmetabolizing gut bacteria using data from the Men’s Lifestyle Validation Study (MLVS) and found that this sulfur microbial diet score, characterized by high intakes of processed meats and low-calorie beverages, was associated with increased risk of distal CRC in men.[6] because there are potential sex-based differences in nutrient metabolism[7] and CRC risk,[8] a study leveraging a more diverse population is needed to confirm these findings. Cohort studies[9,10] and reviews[8,11] have reported that, compared with men, women have a lower overall incidence of CRC but a higher risk of proximal colon cancer, which tends to be more advanced and less differentiated than distal colon cancer.[8,10,12] In addition, there are potential sex differences in the gut microbiome in response to diet.[13,14] For example, a study using an interleukin 10–deficient murine colitis model found that, in male mice, high-dose dietary fiber supplementation was associated with increased microbial alpha diversity and reduced colonic interleukin 12p70, while in female mice, there was no change in alpha diversity, microbial relative abundance, or colonic inflammation markers.[13]

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