Gut microbial characteristics associated with pegylated interferon treatment response in chronic hepatitis B: insights into the gut–liver axis

Background Pegylated interferon (Peg-IFN) treatment response varies considerably among patients with chronic hepatitis B (CHB). The role of the gut microbiota in this heterogeneity remains unclear. This study aimed to characterize gut microbial features associated with Peg-IFN response and explore their potential relevance to the gut–liver axis. Methods A total of 64 patients with CHB who completed 24 weeks of Peg-IFN-based therapy were enrolled in this study. Fecal samples collected at week 24 were analyzed using 16S rRNA gene sequencing. Microbial characteristics and clinical factors associated with treatment response were evaluated, followed by development of an integrated classification model. Results Among the 64 patients, 38 were classified as responders and 26 as non-responders. Responders exhibited distinct gut microbial profiles, characterized by increased microbial richness ( p = 0.014), altered community composition ( p = 0.045), and different microbial interaction patterns. Dorea abundance was enriched in responders and independently associated with treatment response. Multivariable logistic regression identified lower baseline HBsAg levels (OR = 0.562, p = 0.048), higher platelet counts (OR = 1.020, p = 0.007), and increased Dorea abundance (OR = 3.876, p = 0.008) as independent factors associated with response. Restricted cubic spline analysis supported a significant association between Dorea abundance and response probability. The Virological–Host–Microbial (VHM) triad model integrating these factors demonstrated promising apparent discrimination (ROC-AUC = 0.790) and calibration in the development cohort. Conclusion Distinct gut microbial ecological patterns are associated with Peg-IFN treatment response in CHB, with Dorea representing a characteristic microbial feature. This study provides a multidimensional framework for understanding heterogeneity in interferon responsiveness and highlights the potential relevance of the gut–liver–immune axis.