Crosstalk between gut microbiota dysbiosis and mercury-induced hepatointestinal toxicity in mice

As a multi-organ toxic heavy metal, chronic mercury exposure can cause multiple organ damage in mammal. This study aimed to investigate the connection between liver fibrosis and the gut microbiota in the long-term inorganic mercury exposure. Twenty-eight mice were randomly divided into 4 groups (n = 7), which were given different concentrations of mercury (0, 25, 50, 100 mg/L) in drinking water. 16S rRNA gene sequencing of ileal contents, plasma metabolomics, and transcriptomics detection of liver were performed. Biochemical indicators detection, histopathological examination, quantitative real-time PCR, and Western blot assay were conducted to further validate the multi-omics findings. Inorganic mercury exposure disrupts the intestinal barrier and flora balance, which were confirmed by the levels of Bifidobacterium abundance, polyamine concentration, and the endogenous alcohol. Meanwhile, the alteration of blood components affected the metabolic function of the liver, and then leads to cell cycle disorder, oxidative stress, inflammation, and activation of hepatic stellate cells by inhibiting PGC-1α signaling pathway in the mouse liver. In conclusion, long-term inorganic mercury exposure induced liver fibrosis in mice through the microbiota-gut-liver axis. Hence, the modulation of the microbiota-gut-liver axis may be a promising treatment for inorganic mercury-induced liver fibrosis.