Association of gut microbiota dietary index with MAFLD and the risk of liver fibrosis: the mediating effect of vitamins

Abstract Metabolic dysfunction-associated fatty liver disease (MAFLD) is emerging as the leading cause of chronic liver disease worldwide, with a spectrum ranging from simple steatosis to advanced fibrosis and cirrhosis. Its pathogenesis is multifactorial and involves genetic, metabolic, and gut microbiota factors. Gut microbiota, through the gut-liver axis, plays a crucial role in the progression of MAFLD. Here, we investigated the association between DI-GM, a novel metric reflecting diet-microbiota interactions, MAFLD, and liver fibrosis, with a focus on the mediating role of vitamins. Using data from 13,498 participants across seven NHANES cycles (2007–2018), we found that higher DI-GM scores, indicative of a healthier gut microbiota-promoting diet, were associated with a reduced prevalence of MAFLD (OR = 0.93, 95% CI = 0.88–0.99) and high-risk liver fibrosis (OR = 0.94, 95% CI = 0.90–0.98) in fully adjusted models. Notably, the relationship between DI-GM and MAFLD and the risk of liver fibrosis is largely mediated by specific vitamins and carotenoids, with vitamin C and cis-β-carotene emerging as key mediators. These findings suggest that dietary interventions targeting the gut microbiota and vitamin supplementation could offer new strategies for the prevention and management of MAFLD. Our study provides the first comprehensive evidence linking DI-GM to MAFLD and the risk of liver fibrosis, highlighting the potential of diet and nutrition to modulate metabolic liver diseases. Future research should focus on elucidating the underlying mechanisms and validating these findings through prospective studies and clinical trials.