Wang Fengjiao, Wu Yechen, Ni Jiali, Xie Qianhan, Shen Jian, Chen Hui, Ma Chengyu, Yao Yuanyuan, Wang Jinzhi, Xu Lvwan, Xiang Qiangqiang, Zhao Yuxi, Chen Yanfei, Li Lanjuan
Shandong First Medical University, Jinan, China.
Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China.
Microbiol Spectr. 2025 Aug 5;13(8):e0076425. doi: 10.1128/spectrum.00764-25. Epub 2025 Jul 11.
Gut microbiota dysbiosis has been observed in HBV-related cirrhosis, but its role in early-stage disease and its correlation with liver pathology remain unclear. Moreover, whether dysbiosis is a cause or consequence of liver cirrhosis is still debated. We recruited 20 treatment-naïve patients with chronic HBV infection, assessing liver injury via biopsy. Fecal metagenomic sequencing was used to analyze the correlation between gut microbiota and liver histology. To explore the causality, fecal samples from an HBV-related cirrhosis patient were transplanted into mice with CCl₄-induced liver fibrosis. Patients with significant histological damage exhibited reduced alpha diversity and greater microbial homogeneity. Species such as , , and had decreased abundance, while , , and were enriched. Mice receiving fecal transplants from the cirrhotic patient showed aggravated liver fibrosis, with increased collagen deposition; elevated ALT, AST, and ALP levels; and heightened hepatic inflammatory gene expression. Additionally, abnormal bile acid profiles with elevated unconjugated bile acids (e.g., GCA and CA) were observed. Gut microbiota dysbiosis is closely associated with liver histological damage in chronic HBV infection and may drive fibrosis progression via microbial-bile acid interactions. These findings suggest potential for gut microbiota-based assessment and treatment strategies in chronic hepatitis B.IMPORTANCEThis study elucidates a significant association between gut microbiota dysbiosis and liver histological damage in patients with chronic hepatitis B (HBV), potentially exacerbating fibrosis progression through bile acid interactions. By analyzing patient gut microbiota and conducting fecal transplant experiments in mice, researchers have identified that gut microbiota dysbiosis contributes to hepatic fibrosis during chronic HBV infection. These findings underscore the importance of the gut-liver axis in HBV disease progression, indicating that monitoring or modulating gut bacteria may facilitate early diagnosis or therapeutic interventions. This research bridges the gap in understanding whether microbial alterations drive disease progression or result from it, providing a foundation for developing therapies targeting the microbiome to mitigate liver damage in chronic HBV infections.
在乙型肝炎病毒（HBV）相关肝硬化中已观察到肠道微生物群失调，但其在疾病早期阶段的作用及其与肝脏病理学的相关性仍不清楚。此外，肠道微生物群失调是肝硬化的原因还是结果仍存在争议。我们招募了20名未经治疗的慢性HBV感染患者，通过活检评估肝损伤情况。采用粪便宏基因组测序分析肠道微生物群与肝脏组织学之间的相关性。为了探究因果关系，将一名HBV相关肝硬化患者的粪便样本移植到四氯化碳诱导的肝纤维化小鼠体内。具有显著组织学损伤的患者表现出α多样性降低和微生物同质性增加。诸如[具体物种1]、[具体物种2]和[具体物种3]等物种的丰度降低，而[具体物种4]、[具体物种5]和[具体物种6]则富集。接受肝硬化患者粪便移植的小鼠表现出肝纤维化加重，胶原沉积增加；谷丙转氨酶（ALT）、谷草转氨酶（AST）和碱性磷酸酶（ALP）水平升高；肝脏炎症基因表达增强。此外，还观察到胆汁酸谱异常，未结合胆汁酸（如甘氨胆酸和胆酸）升高。肠道微生物群失调与慢性HBV感染中的肝脏组织学损伤密切相关，并可能通过微生物 - 胆汁酸相互作用推动纤维化进展。这些发现表明基于肠道微生物群的评估和治疗策略在慢性乙型肝炎中的潜力。重要性本研究阐明了慢性乙型肝炎（HBV）患者肠道微生物群失调与肝脏组织学损伤之间的显著关联，可能通过胆汁酸相互作用加剧纤维化进展。通过分析患者肠道微生物群并在小鼠中进行粪便移植实验，研究人员发现肠道微生物群失调在慢性HBV感染期间促成肝纤维化。这些发现强调了肠 - 肝轴在HBV疾病进展中的重要性，表明监测或调节肠道细菌可能有助于早期诊断或治疗干预。这项研究弥合了关于微生物改变是驱动疾病进展还是由疾病导致的理解差距，为开发针对微生物群的疗法以减轻慢性HBV感染中的肝损伤提供了基础。
