Chronic lead exposure induces fatty liver disease associated with the variations of gut microbiota

Background: Lead (Pb) has been suggested as an endocrine-disrupting chemical. However, few studies have investigated the association between chronic Pb exposure and fatty liver disease. Objectives: We aimed to investigate the association of chronic Pb exposure with fatty liver disease and whether the variations of the gut microbiota involve in the mechanism of the fatty liver disease induced by chronic Pb exposure. Methods: We conducted a cross-sectional study of 3066 rural participants in East China. Blood lead level (BLL) was detected, and abdominal ultrasonography was used to diagnose hepatic steatosis. Both the definition of non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) were used. Wistar rats were randomly divided into two groups and each group was exposed to 0 or 0.05% w/v Pb through drinking water for 28 weeks. The relevant parameters of hepatic lipid metabolism and gut microbiota were analyzed. Results: In humans, after adjusting for potential confounders, the odds of having NAFLD and MAFLD were significantly increased by 54% and 52% in the participants in the fourth BLL quartile (OR 1.54, 95% CI 1.24, 1.91 and OR 1.52, 95% CI 1.22, 1.89). In the rats, chronic Pb exposure induced the increased visceral fat, hepatic steatosis, and dysbiosis of the gut microbiota, including the decrease of richness, diversity, evenness and phylogenetic diversity of the gut microbiota and the significant alternations of the gut microbiota composition, particularly, the decrease of the relative abundance of Coprococcus and Oscillospira at the genus level. Conclusions: Chronic Pb exposure could induce fatty liver disease, which may be associated with the variations of the gut microbiota.