Fecal microbiota from hepatitis B-infected individuals alters triglyceride metabolism and microbial pathways in mice

Abstract Background This study investigates the impact of chronic hepatitis B virus infection on triglyceride metabolism through alterations in the gut microbiome, using a faecal microbiota transplantation (FMT) mouse model. Methods This shotgun metagenomic analysis was conducted using stored samples from a previously published FMT experiment. Nineteen mice with sufficient faecal DNA for sequencing were included, comprising ten mice transplanted with microbiota from two hepatitis B virus (HBV)-infected donors and nine mice transplanted with microbiota from two non-infected donors. Shotgun metagenomic sequencing was performed on stool collected two weeks post-FMT, and metabolic parameters were compared between two and five weeks post-transplantation. Results Mice receiving microbiota from HBV-infected individuals exhibited lower triglyceride levels (100.05 ± 10.82 vs. 111.69 ± 12.27 mg/dL, p = 0.04) at five weeks post-FMT compared with those receiving microbiota from non-infected individuals. HBV-positive mice also showed higher microbial diversity and an increased abundance of short-chain fatty acid–producing bacterial species, including Anaerofustis stercorihominis, Bacteroides cellulosilyticus, and Butyricimonas virosa. Shotgun analysis revealed reduced activity in the pentose phosphate pathway and galactitol degradation pathways, both involved in carbohydrate and fatty acid metabolism, alongside unique bile acid dihydroxylation pathways. Conclusions These findings indicate that gut microbiota with chronic HBV infection modulate host lipid metabolism, particularly triglyceride levels, through distinct microbial species and metabolic pathways.