A dietary pattern promoting gut sulfur metabolism is associated with increased mortality and altered circulating metabolites in low-income American adults

Abstract

Background: Excessive hydrogen sulfide in the gut, generated by sulfur-metabolising bacteria from foods, has been linked to intestinal inflammation and human diseases. We aim to investigate the interplay between diet and sulphur-metabolising bacteria in relation to mortality and circulating metabolites in understudied populations.

Methods: In the Southern Community Cohort Study (SCCS), a prospective cohort of primarily low-income American adults, habitual diets were assessed using a food frequency questionnaire at baseline (2002-2009). A sulfur microbial diet score (SMDS) was developed among 514 Black/African American participants by linking habitual dietary intakes with the abundance of sulfur-metabolising bacteria profiled by faecal shotgun metagenomics. The SMDS was then constructed among all eligible SCCS participants (50,114 Black/African American and 23,923 non-Hispanic White adults), and its associations with mortality outcomes were examined by Cox proportional hazards model and Fine-Grey subdistribution hazard model. The association between SMDS and 1110 circulating metabolites was examined by linear regression among 1688 SCCS participants with untargeted metabolomic profiling of baseline plasma samples.

Findings: Over an average 13.9-year follow-up, SMDS was associated with increased all-cause mortality (HR [95% CI] for the highest vs. lowest quartiles: 1.21 [1.15-1.27]) and cardiovascular disease (1.18 [1.08-1.29]), cancer (1.13 [1.02-1.25]), and gastrointestinal cancer-specific (1.22 [1.00-1.49]) mortality among Black/African American participants (all P-trend<0.05). The associations were largely consistent across participant subgroups. Similar results were observed among non-Hispanic White participants. The SMDS was associated with 112 circulating metabolites, which mediated 36.15% of the SMDS-mortality association (P = 0.002).

Interpretation: A dietary pattern promoting sulfur-metabolising gut bacteria may contribute to increased total and disease mortality in low-income American adults.

Funding: This study was funded by the National Institutes of Health, United States, to Vanderbilt University Medical Center, United States, and Anne Potter Wilson Chair endowment to Vanderbilt University, United States.

Keywords: Dietary patterns; Gut microbiota; Low-income population; Metabolomics; Prospective studies; Racial minorities.