慢性乙型肝炎患者HBeAg阴性与阳性者肠道微生物群的差异及替诺福韦艾拉酚胺对肠道菌群的影响
Difference of gut microbiota between patients with negative and positive HBeAg in chronic hepatitis B and the effect of tenofovir alafenamide on intestinal flora.
作者信息
Long Jianfei, Gong Jingru, Zhu Han, Liu Xiaolin, Li Ling, Chen Bicui, Ren Hongyan, Liu Chao, Lu Huiping, Zhang Jiming, Wang Bin
机构信息
Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
Department of Pharmacy, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
出版信息
Front Microbiol. 2023 Sep 20;14:1232180. doi: 10.3389/fmicb.2023.1232180. eCollection 2023.
BACKGROUND
Severe liver diseases, such as liver fibrosis, cirrhosis, and liver cancer, are mainly caused by hepatitis B virus (HBV). This study investigated the differences between gut microbiota in HBeAg-positive and negative groups of patients with chronic hepatitis B (CHB) and investigated the effect of tenofovir alafenamide (TAF) on gut microbiota.
METHODS
This prospective study included patients with CHB not taking nucleoside antivirals (No-NAs group, = 95) and those taking TAF (TAF group, = 60). We divided CHB patients into two groups according to the HBeAg status of the subjects on the day of data collection. Phase 1 are HBeAg-negative patients and phase 2 are HBeAg-positive patients. We investigated the improvement of clinical symptoms by TAF, as well as differences in gut microbiota between different groups by 16S rRNA high-throughput sequencing.
RESULTS
Gut microbiota demonstrated significant differences between patients with HBeAg-positive and -negative CHB. Both the No-NAs and TAF Phase 2 subgroups demonstrated significantly increased microbiota richness and diversity, showing greater heterogeneity. Additionally, the Phase 2 subgroup exhibited a low abundance of pathways associated with glucose metabolism and amino acid metabolism. The TAF group demonstrated a significantly decreased HBV load, alanine aminotransferase, and aspartate aminotransferase and a significant increase in prealbumin compared with the No-NAs group. No significant difference was found in uric acid, creatinine, blood calcium, inorganic phosphorus, eGFR, and β2-microglobulin concentrations between the two groups. Additionally, the urea level in the TAF group was significantly lower than that in the No-NAs group, but with no significant effect on other indicators such as eGFR and β2-microglobulin.
CONCLUSION
This study revealed significant differences in gut microbiota composition and function between patients with HBeAg-positive and -negative CHB.
背景
严重的肝脏疾病，如肝纤维化、肝硬化和肝癌，主要由乙型肝炎病毒（HBV）引起。本研究调查了慢性乙型肝炎（CHB）患者HBeAg阳性和阴性组肠道微生物群的差异，并研究了替诺福韦艾拉酚胺（TAF）对肠道微生物群的影响。
方法
这项前瞻性研究纳入了未服用核苷类抗病毒药物的CHB患者（未服用核苷类药物组，n = 95）和服用TAF的患者（TAF组，n = 60）。我们根据数据收集当天受试者的HBeAg状态将CHB患者分为两组。第1阶段为HBeAg阴性患者，第2阶段为HBeAg阳性患者。我们研究了TAF对临床症状的改善情况，以及通过16S rRNA高通量测序研究不同组之间肠道微生物群的差异。
结果
HBeAg阳性和阴性的CHB患者肠道微生物群存在显著差异。未服用核苷类药物组和TAF第2亚组的微生物群丰富度和多样性均显著增加，表现出更大的异质性。此外，第2亚组与葡萄糖代谢和氨基酸代谢相关的通路丰度较低。与未服用核苷类药物组相比，TAF组的HBV载量、丙氨酸氨基转移酶和天冬氨酸氨基转移酶显著降低，前白蛋白显著升高。两组之间尿酸、肌酐、血钙、无机磷、估算肾小球滤过率和β2-微球蛋白浓度无显著差异。此外，TAF组的尿素水平显著低于未服用核苷类药物组，但对估算肾小球滤过率和β2-微球蛋白等其他指标无显著影响。
结论
本研究揭示了HBeAg阳性和阴性CHB患者肠道微生物群组成和功能的显著差异。
Zotero 插件