Effect of hepatocyte FXR on gut microbiota mice infected with Schistosoma japonicum

Objective To analyze the effect of farnesoid X receptor(FXR) specific knockout in hepatocytes on the gut microbiota of mice infected with Schistosoma japonicum(S. japonicum).Methods Male C57BL/6J and hepatocyte-specific FXR KO(FXR-HKO) mice, aged 6-8 weeks, were randomly divided into four groups: a wild-type normal control group(WT, n=5), a FXR-HKO normal control group(FXR-HKO, n=6), a wild-type infected group(Sj-WT, n=6), and a FXR-HKO infected group(Sj-FXR-HKO, n=5). Mice in the infected group were infected with(15±1) cercaria of S. japonicum, and sacrificed on week 5 after infection. The colon contents were collected under sterile conditions for analyzing the diversity and abundance of gut microbiota by 16S rDNA sequencing.Results According to Beta diversity analysis, there were apparently differences in the gut microbiota between the Sj-WT group and the Sj-FXR-HKO group. At the phylum level, compared with the WT group, the Sj-WT group and Sj-FXR-HKO group showed increases in the abundance of Bacteroides significantly and decreases in the abundance of Firmicutes, with a reduced abundance ratio of Firmicutes and Bacteroides(P<0.05). At the genus level, compared with the WT group, the abundance of Bacteroides significantly increased in the gut microbiota of mice infected with S. japonicum(P<0.05). The abundance of Bacteroides in the Sj-FXR-HKO group was higher than that in the Sj-WT group(P<0.05). The abundances of Desulfovibrio, Dubosiella and Lactobacillus significantly decreased in the Sj-WT group(P<0.05), while the abundances of uncultured_bacterium_f_Ruminococcaceae, Lachnospiraceae_NK4A136_group, Dubosiella and Lactobacillus significantly decreased in the Sj-FXR-HKO group(P<0.05).Conclusions FXR-specific knockout in hepatocyte affects the homeostasis of gut microbiota in mice infected with S. japonicum. These findings provide a solid experimental foundation for further investigating the role and mechanism of FXR-gut microbiota in schistosomiasis.