Table_1_Featured Gut Microbiomes Associated With the Progression of Chronic Hepatitis B Disease.xlsx

Dysbiosis of gut microbiota during the progression of HBV-related liver disease is not well understood, as there are very few reports that discuss the featured bacterial taxa in different stages. The aim of this study was to reveal the featured bacterial species whose abundances are directly associated with HBV disease progression, that is, progression from healthy subjects to, chronic HBV infection, chronic hepatitis B to liver cirrhosis. Approximately 400 fecal samples were collected, and 97 samples were subjected to 16S rRNA gene sequencing after age and BMI matching. Compared with the healthy individuals, significant gut microbiota alterations were associated with the progression of liver disease. LEfSe results showed that the HBV infected patients had higher Fusobacteria, Veillonella, and Haemophilus abundance while the healthy individuals had higher levels of Prevotella and Phascolarctobacterium. Indicator analysis revealed that 57 OTUs changed as the disease progressed, and their combination produced an AUC value of 90% (95% CI: 86–94%) between the LC and non-LC groups. In addition, the abundances of OTU51 (Dialister succinatiphilus) and OTU50 (Alistipes onderdonkii) decreased as the disease progressed, and these results were further verified by qPCR. The LC patients had the higher bacterial network complexity, which was accompanied with a lower abundance of potential beneficial bacterial taxa, such as Dialister and Alistipes, while they had a higher abundance of pathogenic species within Actinobacteria. The compositional and network changes in the gut microbiota in varied CHB stages, suggest the potential contributions of gut microbiota in CHB disease progression.

乙型肝炎病毒（HBV）相关肝病进展过程中的肠道菌群失调机制尚未完全阐明，目前鲜有研究探讨不同疾病阶段的特征性细菌类群。本研究旨在明确与HBV相关肝病进展直接相关的特征性细菌物种，即从健康个体到慢性HBV感染、再由慢性乙型肝炎进展至肝硬化过程中丰度发生变化的细菌类群。本研究共收集约400份粪便样本，经年龄与身体质量指数（BMI）匹配后，选取97份样本进行16S rRNA基因测序。与健康个体相比，肝病进展过程中伴随显著的肠道菌群结构改变。线性判别分析效应大小（LEfSe）分析结果显示，HBV感染者的梭杆菌属（Fusobacteria）、韦荣球菌属（Veillonella）及嗜血杆菌属（Haemophilus）丰度更高，而健康个体的普雷沃氏菌属（Prevotella）与考拉杆菌属（Phascolarctobacterium）丰度更高。指示物种分析显示，随着疾病进展共有57个操作分类单元（OTU）丰度发生显著变化，将这些OTU联合用于区分肝硬化（LC）与非肝硬化组时，其曲线下面积（AUC）可达90%（95%置信区间CI：86%~94%）。此外，OTU51（Dialister succinatiphilus）与OTU50（Alistipes onderdonkii）的丰度随疾病进展持续降低，该结果经实时定量PCR（qPCR）验证得以进一步确认。肝硬化患者的肠道菌群网络复杂度更高，同时伴随潜在有益菌属丰度降低，例如戴阿利斯特杆菌属（Dialister）与另枝菌属（Alistipes），而其放线菌门（Actinobacteria）内的病原菌丰度则更高。不同慢性乙型肝炎（CHB）阶段的肠道菌群组成与网络结构变化，提示肠道菌群可能在慢性乙型肝炎疾病进展中发挥潜在作用。