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

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. We aimed to investigate whether consuming the sulfur microbial diet is associated with nonalcoholic fatty liver disease (NAFLD). 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 β-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. 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 = 0.044). 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.