Understanding the hepatoxicity of inorganic mercury through guts: Perturbance to gut microbiota, alteration of gut-liver axis related metabolites and damage to gut integrity

Mercury (Hg) brings adverse effects to the environment and human beings and inorganic mercury (IHg) is a typical hepatic toxin. This work studied the impacts of IHg on gut microbes and metabolome together with its damage to liver and gut in rats through gut microbiome, metabolomics and metallomics. Sprague Dawley (SD) rats were orally exposed to 0.4 μg/mL IHg and sacrificed after 24 h. It was found that IHg perturbed greatly on the gut microbiota, such as increased pathogenic bacteria like G. bacillus. In addition, IHg also changed gut-liver axis related metabolites, which was confirmed by the secretion of a large number of inflammatory factors in both the gut and the liver. The changed gut-liver axis related metabolites correlated well to the changes of gut microbiome. In all, besides the direct deposition in liver of Hg, the perturbance to gut microbiome and alteration of gut-liver axis related metabolites by IHg also contributed to its hepatoxicity, which provides new insights about the hepatoxicity of chemicals. The strategy applied in this work may also be used to understand the hepatoxicity of other chemicals. •IHg perturbs gut microbiome including the increased pathogenic bacteria.•IHg alters gut-liver axis related metabolites.•The changes of gut-liver axis related metabolites correlates well with the perturbance of gut microbiome.•The perturbance of gut microbiome and gut-liver axis related metabolites contributes to the hepatoxicity of IHg.