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

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.