Species-level enterosignatures predict clinical phenotypes in chronic hepatitis B and causal triangulation of gut-metabolite-CHB interactions

作者：Tingting Yuan, Jiali Chen, H. J. Yang, Lian‐Feng Li, Shan Lu, Ji Pu, Yamin Sun, Wenchao Lin, Lu Yu, Zhaoqin Zhu, Han Zheng, Jianguo Xu · 发表于：Frontiers in Microbiology · 年份：2025 · DOI：10.3389/fmicb.2025.1683451 · 被引用次数：3 · 研究领域：Gut microbiota and health、Clostridium difficile and Clostridium perfringens research、Hepatitis B Virus Studies

Chronic hepatitis B (CHB) remains a significant global health challenge, with research indicating the gut microbiota’s influence on disease progression, although investigations have primarily been limited to the genus level. This study conducted species-level research using the Human Gut Microbiome Analysis Database (HGMAD) to examine differences in gut microbiota between CHB patients and healthy controls (HC), to investigate enterotype associations with CHB, to assess the predictive capacity of enterosignatures for CHB phenotypes, and to determine causal relationships among gut microbiota, metabolites, and CHB. The cross-sectional investigation included 129 CHB patients and 58 HC, with fecal samples analyzed by 16S rRNA gene sequencing of the V3–V4 region. Significant differences in α-diversity and β-diversity ( P < 0.05) were observed between the CHB and HC groups. Taxonomic analysis revealed that the high prevalent bacteria group was lower in CHB patients (61.15%) than in HC (98.05%), indicating increased gut microbiota heterogeneity in CHB. Among known bacterial species, pathogens showed higher prevalence in CHB patients (22.80% vs. 11.49%), with several potential enteropathogenic bacteria (e.g., Bacteroides fragilis and Haemophilus parainfluenzae ) enriched in CHB. Dimensionality reduction and clustering analysis of gut microbiota in CHB patients revealed two distinct enterotypes: ET-P dominated by Prevotella and ET-B dominated by Bacteroides . ET-P demonstrated a...