Intestinal microbiota dysbiosis contributed to the development of subchronic liver damage in arsenic-exposed mice

There is an extensive amount of evidence that links changes in the intestinal microbiota structure to the progression and pathophysiology of many liver diseases. However, comprehensive analysis of gut flora dysbiosis in arsenic-induced hepatotoxicity is lacking. Herein, C57BL/6 mice were exposed to arsenic (1, 2, or 4 mg/kg) for 12 weeks, after which faecal microbiota transplantation (FMT) study was conducted to confirm the roles of the intestinal microbiome in pathology. Treatment with arsenic resulted in pathological and histological changes in the livers such as inflammatory cell infiltration and decreased levels of TP and CHE but increased levels of ALP, GGT, TBA, AST, and ALT. Arsenic caused an increase in the relative abundance of Escherichia-Shigella, Klebsiella, and Blautia. However, decreases in Muribaculum and Lactobacillus. In arsenic exposed mice, protein expressions of Occludin, ZO-1, and MUC2 were significantly decreased, the level of FITC in serum was increased, and FITC fluorescence was extensively dispersed in the intestinal tract. Importantly, FMT experiments showed that mice gavaged with stool from arsenic-treated mice exhibited severe inflammatory cell infiltration in liver tissues. Arsenic-manipulated gut microbiota transplantation markedly facilitated gut flora dysbiosis in the recipient mice, including an up-regulation in Escherichia-Shigella and Bacteroides, and a down-regulation in Lactobacillus and Desulfovibrio. In parallel with the intestinal microbiota wreck, protein expressions of Occludin, ZO-1, and MUC2 was decreased. Our findings suggested that subchronic exposure to arsenic can affect the homeostasis of the intestinal microbiota, induce intestinal barrier dysfunction, increase intestinal permeability, and cause damage to liver tissues in mice.