The gut microbiome mediates the association between a flavonoid-rich diet and MASLD in a population-level analysis.

PURPOSE: A growing body of evidence suggests diets rich in flavonoids may protect against metabolic-dysfunction associated steatotic liver disease (MASLD) development and progression. As the gut microbiome is important in the biotransformation of flavonoids to their constituent bioactive metabolites, studies on the potential mediating role of the gut microbiome in the association between dietary flavonoid intakes and MASLD are warranted but lacking. Thus, this study aims to examine the associations between a diet rich in flavonoids and MASLD, and assess the potential mediating role of the gut microbiome. METHODS: In a cross-sectional analysis (n = 531), using the FlavoDiet score (FDS), we assessed the association between a flavonoid-rich diet and MASLD (ascertained by magnetic resonance imaging) using multivariable logistic and linear regression. Additionally, we used mediation analysis to identify and assess potential 16S-derived gut microbiome mediators. RESULTS: Each doubling of the FDS was associated with a 27% lower odds of MASLD (OR: 0.73 [95% CI 0.54-0.98], p = 0.04) after multivariable adjustment. 9.2% of this association was mediated by a greater abundance of the genus Eisenbergiella (indirect effect ß = - 0.006 [95% CI - 0.019, to - 0.000], p = 0.04). CONCLUSION: These findings suggest that a flavonoid-rich diet is associated with better liver health, and that the abundance of the Eisenbergiella taxa may in part explain the association between a flavonoid-rich diet and MASLD.