Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, Fujian, China.
School of Statistics, University of International Business and Economics, Chaoyang District, Beijing, China.
Sci Rep. 2021 Feb 5;11(1):3253. doi: 10.1038/s41598-021-82939-1.
Tenofovir and entecavir are currently designated as the preferred oral antiviral drugs for chronic hepatitis B. However, only less than 40% of patients can achieve HBeAg seroconversion. We aim at investigating the role of intestinal microbiome in HBeAg seroconversion induced by oral antiviral therapy and describe multi-omics characteristics of HBeAg seroconversion associated intestinal flora. In this study, we prospectively collected fecal samples at baseline from the patients with HBeAg positive chronic hepatitis B who would have oral antiviral therapy. 16S rDNA sequencing and metabolomics were performed. We identified HBeAg seroconversion-related microbial signature and constructed prediction model for HBeAg seroconversion. Thirty-seven of these subjects achieved HBeAg seroconversion within 156 weeks after the initiation of oral antiviral therapy, while 41 subjects remained HBeAg positive even after over 156 weeks of therapy. A computational statistical and machine learning approach allowed us to identify a microbial signature for HBeAg seroconversion. Using random forest method, we further constructed a classifier based on the microbial signature, with area under curve being 0.749 for the test set. Patients who achieved HBeAg seroconversion tended to have lower abundance of certain fecal metabolites such as essential amino acids, and several dipeptides. By analyzing the fecal microbiota from the patients with and without HBeAg seroconversion, we showed intestinal microbiome play a critical role in HBeAg seroconversion induced by oral antiviral therapy. We also identified intestinal microbial signature that is associated with HBeAg seroconversion after oral antiviral therapy.
替诺福韦和恩替卡韦目前被指定为慢性乙型肝炎的首选口服抗病毒药物。然而，只有不到 40%的患者可以实现 HBeAg 血清学转换。我们旨在研究肠道微生物组在口服抗病毒治疗诱导的 HBeAg 血清学转换中的作用，并描述与 HBeAg 血清学转换相关的肠道菌群的多组学特征。在这项研究中，我们前瞻性地收集了 HBeAg 阳性慢性乙型肝炎患者口服抗病毒治疗前的粪便样本。进行了 16S rDNA 测序和代谢组学分析。我们确定了与 HBeAg 血清学转换相关的微生物特征，并构建了 HBeAg 血清学转换的预测模型。在开始口服抗病毒治疗后的 156 周内，其中 37 名患者实现了 HBeAg 血清学转换，而 41 名患者即使在 156 周以上的治疗后仍保持 HBeAg 阳性。计算统计和机器学习方法使我们能够识别出与 HBeAg 血清学转换相关的微生物特征。使用随机森林方法，我们进一步基于微生物特征构建了一个分类器，测试集的曲线下面积为 0.749。实现 HBeAg 血清学转换的患者往往具有较低的某些粪便代谢物（如必需氨基酸和几种二肽）的丰度。通过分析 HBeAg 血清学转换患者和未转换患者的粪便微生物组，我们表明肠道微生物组在口服抗病毒治疗诱导的 HBeAg 血清学转换中起着关键作用。我们还确定了与口服抗病毒治疗后 HBeAg 血清学转换相关的肠道微生物特征。
