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Background:  Hepatitis B virus (HBV) infection has been reported to affect the bacterial characteristics in the host. We aimed to elucidate the compositional and functional characteristics of the microbiota in southern Chinese patients with coexistent HBV infection, non-alcoholic fatty liver disease (NAFLD), and type-2 diabetes mellitus (T2DM).   Methods:  Healthy controls (HCs) and patients with coexistent NAFLD and T2DM were enrolled. Patients were divided into two groups: N1 (without HBV infection) and N2 (with HBV infection). Stool samples were collected for 16s RNA gene sequencing and untargeted metabolomics analysis.   Results:  Bacterial diversity was decreased in the N2 group. There was a significantly lower abundance of bacteria of  Faecalibacterium, Gemmiger , and  Clostridium_XIVA  genera, but a higher abundance of  Megamonas  and  Phascolarctobacterium  genera in the N2 group. Compared with the N1 group, the abundance of  Gemmiger  species was even lower, and alterations in the abundance of  Phascolarctobacterium  and  Clostridium_XIVA  genera only occurred in the N2 group. There were significantly different fecal metabolic features, which were enriched in glucose and lipid metabolic pathways (e.g., fatty acid and glycerophospholipid metabolism) between the N2 and HC groups. Metabolites in glycerophospholipid metabolism, such as Sn-3-o-(geranylgeranyl)glycerol1-phosphate, were even higher in the N2 group than in the N1 group. The decreased  Faecalibacterium  and  Gemmiger  contributed to the increased level of Sn-3-o-(geranylgeranyl) glycerol1-phosphate, palmitoylcarnitine, and serum triglycerides.  Clostridium_XIVA  species were positively correlated to 15(s)-hpete.  Megamonas  species were positively correlated with the serum level of glucose indirectly.   Conclusions:  The distinct gut-microbiome profile associated with HBV infection has a role in lipid metabolism and glucose metabolism in patients with coexistent NAFLD and T2DM.   Clinical Trial Registration:  www.ClinicalTrials.gov , identifier: NCT03525769.

frontiers in medicine

Alterations in the Gut Microbiota and Hepatitis-B-Virus Infection in Southern Chinese Patients With Coexisting Non-Alcoholic Fatty Liver Disease and Type-2 Diabetes Mellitus