The sulfur microbial diet and risk of nonalcoholic fatty liver disease: a prospective gene-diet study from the UK Biobank

Background: The gut microbiota is closely related to liver diseases. The dietary pattern associated with sulfur -metabolizing bacteria in stool has been found to influence intestinal health. Objective: We aimed to investigate whether consuming the sulfur microbial diet is associated with nonalcoholic fatty liver disease (NAFLD). Methods: We included 143,918 participants of European descent from the UK Biobank. Information on serving sizes used per diet component was recorded by an online 24-h dietary assessment tool (Oxford WebQ). The total sulfur microbial diet score was constructed by summing the product of beta-coefficients and corresponding serving sizes. NAFLD was ascertained using hospital inpatient and death records. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Mediation analyses were used to investigate underlying mediators including body mass index, waist circumference, glucose, triglyceride, urate, and C -reactive protein. A polygenic risk score for NAFLD was constructed and stratified to assess whether the association is modified by genetic predisposition. Results: After a median follow-up of 11.7 y (interquartile range: 11.3-12.5 y), we documented 1540 incident cases of NAFLD. After adjustment for covariates, we observed an overall J -shaped relationship between the sulfur microbial diet and risk of NAFLD. Those in the highest quartile of sulfur microbial diet score had a 46% increased risk of NAFLD [HRQ4vsQ1 (95% CI): 1.46 (1.26, 1.69)]. We also found that this association is partly mediated by metabolic disorders and systemic inflammation. In addition, the positive association was stronger among individuals at higher genetic risk for NAFLD (Pinteraction 1/4 0.044). Conclusions: The sulfur microbial diet had adverse associations with incident NAFLD, particularly in those at a higher genetic risk. Our study may provide evidence on the role of sulfur -metabolizing bacteria in the diet-NAFLD association.