Dysbiosis of gut fungi and bacteria in patients with HBV with low-level viremia compared with sustained virologic responders and healthy controls

Abstract

Although bacterial dysbiosis in chronic hepatitis B (CHB) is well established, the role of the gut mycobiome-particularly its functional interplay with bacteria during virological remission versus treatment failure remains unexplored. In this study, the gut bacteriome and mycobiome were characterized in hepatitis B virus (HBV) patients with low-level viremia (LLV) or sustained virological response (SVR) and healthy controls (HCs). This study enrolled a cohort comprising 28 healthy controls (HCs) and 43 patients with CHB from the Second Affiliated Hospital of Hainan Medical University. The patients with CHB were further stratified into LLV ( n = 22) and SVR ( n = 21) groups. The bacterial and fungal compositions of the collected fecal samples were characterized by 16 S rRNA gene sequencing and internal transcribed spacer (ITS) sequencing, respectively. Compared with HCs, patients with CHB presented increased bacterial richness but decreased fungal richness. Beta diversity analysis revealed distinct microbial clustering between the HC and CHB groups (LLV and SVR). Patients with LLV showed enrichment of Bacteroides / Faecalibacterium and depletion of Blautia (vs. HCs) as well as lower levels of Lactobacillus and higher levels of Faecalibacterium (vs. patients with SVR). Fungal taxa such as Kazachstania were reduced in the LLV group compared with the HC group, and Candida was less abundant in the LLV group than in the SVR group. A diagnostic model based on the Eubacterium coprostanoligenes grouping variable , Actinomyces , Bacteroides , Lachnoclostridium , and Phascolarctobacterium achieved high accuracy (AUC = 0.804) in distinguishing patients with LLV from HCs. Compared with patients with SVR and HCs, patients with HBV with LLV exhibit distinct gut bacterial and fungal dysbiosis.