Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications:Molecular mechanisms and therapeutic inventions

Hepatitis B virus(HBV)has posed a threat to public health,mainly resulting in liver damage.With long-term accumulation of extracellular matrix,patients with chronic hepatitis B are at high risk of developing into liver fibrosis and cirrhosis and even life-threatening hepatic carcinoma.The occurrence of complications such as spontaneous bacterial peritonitis and hepatic encephalopathy greatly increases disability and mortality.With deeper understanding of the bidirectional interaction between the liver and the gut(gut-liver axis),there is a growing consensus that the human health closely relates to the gut microbiota.Supported by animal and human studies,the gut microbiota alters as the HBV-related liver fibrosis initials and progresses,characterized as the decrease of the ratio between“good”and“potentially pathogenic”microbes.When the primary disease is controlled via antiviral treatment,the gut microbiota dysfunction tends to be improved.Conversely,the recovery of gut microbiota can promote the regression of liver fibrosis.Therapeutic strategies targeted on gut microbiota(rifaximin,probiotics,engineered probiotics and fecal microbiota transplantation)have been applied to animal models and patients,obtaining satisfactory results.