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.

汞（Hg）给环境和人类带来不利影响，无机汞（IHg）是一种典型的肝脏毒素。这项工作通过肠道微生物组、代谢组学和金属组学研究了 IHg 对肠道微生物和代谢组的影响以及对大鼠肝脏和肠道的损害。Sprague Dawley (SD) 大鼠口服暴露于 0.4 μg/mL IHg 并在 24 小时后处死。发现 IHg 极大地扰乱了肠道微生物群，例如增加了G. bacillus等致病菌. 此外，IHg还改变了肠-肝轴相关代谢物，这一点由肠道和肝脏中大量炎症因子的分泌得到证实。改变的肠肝轴相关代谢物与肠道微生物组的变化密切相关。总之，除了汞在肝脏中的直接沉积外，IHg 对肠道微生物组的干扰和肠肝轴相关代谢物的改变也有助于其肝毒性，这为化学物质的肝毒性提供了新的见解。这项工作中应用的策略也可用于了解其他化学品的肝毒性。