Effect of intestinal microbiota imbalance associated with chronic hepatitis B virus infection on the expression of microRNA‑192 and GLP‑1.

It has been reported that hepatitis B virus (HBV) infection has an impact on intestinal microbiota imbalance to induce diabetes mellitus (DM), but the underlying mechanisms still remain to be explored. The present study aimed to investigate the regulatory role of microRNA‑192 (miR‑192‑5p) and glucagon‑like peptide‑1 (GLP‑1) in intestinal microbiota imbalance by recruiting patients with DM infected with HBV. In the present study, patients with HBV infection and different levels of alanine transaminase (ALT) were recruited and divided into three groups. Intestinal microbiota analysis was performed to evaluate the fecal bacterial composition of patients in various groups. Quantitative PCR was performed to explore the differential expression of miR‑192‑5p and GLP‑1 in the feces, peripheral blood and intestinal mucosal tissue samples of each patient. Immunohistochemistry was used to assess the expression of GLP‑1 protein in the intestinal mucosal tissue samples. Luciferase assays were performed by cell transfection of miR‑192‑5p mimics/precursors/inhibitors to study the inhibitory effect of miR‑192‑5p on GLP‑1 expression. Intestinal microbiota imbalance was observed in hepatitis B surface antigen (HBsAg)‑positive patients with high ALT. The expression of miR‑192‑5p was significantly elevated in the feces, peripheral blood and intestinal mucosal tissue samples of HBsAg‑positive patients with high ALT along with decreased GLP‑1 mRNA and protein expression. Luciferase activity of GLP‑1 vector was inhibited by miR‑192‑5p mimics and promoted by miR‑192‑5p inhibitors. Transfection of miR‑192‑5p precursors resulted in upregulation of miR‑192‑5p and downregulation of GLP‑1, while miR‑192‑5p inhibitors remarkably suppressed the expression of miR‑192‑5p and notably induced the expression of GLP‑1. These results showed a regulatory network involving HBV infection, intestinal microbiota imbalance, and miR‑192‑5p and GLP‑1 expression.