Altered faecal microbiota on the expression of Th cells responses in the exacerbation of patients with hepatitis E infection

Fulminant hepatitis E may lead to acute liver failure (ALF). Perturbations of intestinal microbiota are related to severe liver disease. To study the correlations between faecal microbiota and the occurrence and exacerbation of hepatitis E virus (HEV) infection, we characterized 24 faecal samples from 12 patients with acute hepatitis E (AHE) and 12 patients with HEV-ALF using high-throughput sequencing. We found both the alpha and beta diversity indices showed no significant differences between the AHE and HEV-ALF groups. Several predominant taxa were significantly different between the AHE and HEV-ALF groups. Most notably, the HEV-ALF group had increased levels of Gammaproteobacteria, Proteobacteria, Xanthomonadceae and Stenotrophomonas, but reduced levels of Firmicutes, Streptococcus, Subdoligranulum and Lactobacillus, compared with the AHE group. The levels of Lactobacillaceae and Gammaproteobacteria could be used to distinguish patients with HEV-ALF from those with AHE. In addition, the level of Th lymphocytes was significantly lower in the HEV-ALF group than in the AHE group. The relative abundances of Lactobacillaceae and Gammaproteobacteria were positively correlated with Th lymphocytes, serum international normalized ratio (INR) and hepatic encephalopathy severity. Moreover, surviving patients had higher levels of Lactobacillus mucosae than deceased patients. Our study demonstrated that the presence of altered faecal microbiota is associated with exacerbation of HEV infection; this finding may be useful for exploring the interactions among faecal microbiota, immune responses, mechanisms of infection and progression in patients with HEV, as well as for the development of novel diagnostic and therapeutic strategies.