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

Abstract

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e17. Learning Objective: Upon completion of this CME activity successful learners will be able to identify the dietary determinants of sulfurmetabolizing bacteria in humans and whether intake of these foods is associated with risk of colorectal cancer. BACKGROUND & AIMS:Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide (H 2 S), have been associated with development of colorectal cancer (CRC). We identified a dietary pattern associated with sulfurmetabolizing 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 ¼ 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 ¼ .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 ¼ .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.

Methionine Restriction Regulates Cognitive Function in High‐Fat Diet‐Fed Mice: Roles of Diurnal Rhythms of SCFAs Producing‐ and Inflammation‐Related Microbes

“…[49] Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide, have been induced colorectal cancer. [50] The Desulfovibrionales abundance was decreased in the HFD+MR group. Current evidence indicates that the relative abundance of TM7 is increased in Bmal1 −/− mice, which suggests that circadian disorders could influence the gut microbiota.…”

Gut Microbiota-Mediated Inflammation and Gut Permeability in Patients with Obesity and Colorectal Cancer

“…Moreover, a significant over-representation of genes for energy metabolism such as oxidative phosphorylation, methane metabolism, and sulfur metabolism as well as for lipopolysaccharide biosynthesis were found increase in OB-CRC patients with respect to L-CRC patients and L-HC controls. Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide (H 2 S), have been previously associated with development of CRC [ 57 ]. Moreover, gut-derived H 2 S may fragment the mucus bilayer of the gastrointestinal tract and this breach may precede tumorigenesis by exposing gut epithelium to immunogenic luminal bacteria [ 58 ].…”

<p>Progress in Research on Colorectal Cancer-Related Microorganisms and Metabolites</p>

“…Furthermore, the detoxification capacity of the colon tissue for hydrogen sulfide in CRC patients was weakened. 51 Hydrogen sulfide induces the formation of colon cancer mainly through the induction of DNA damage, the release of free radicals, inflammation of the colonic mucosa, excessive colonic mucosa hyperplasia, and inhibiting cytochrome oxidase, butyrate utilization, mucus synthesis, and DNA methylation. 52…”