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替诺福韦酯在乙型肝炎病毒感染诱导的肠道菌群失调恢复中的作用。

Role of tenofovir dipivoxil in gut microbiota recovery from HBV-infection induced dysbiosis.

机构信息

Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

BMC Microbiol. 2024 Sep 20;24(1):359. doi: 10.1186/s12866-024-03457-4.

DOI:10.1186/s12866-024-03457-4
PMID:39304810
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11414042/
Abstract

BACKGROUND

Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF.

RESULTS

The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups.

CONCLUSIONS

This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.

摘要

背景

研究发现,乙型肝炎病毒(HBV)感染者的肠道微生物群落失调。替诺福韦二吡呋酯(TDF)是治疗慢性乙型肝炎(CHB)的首选口服抗病毒药物之一,但 TDF 对患者肠道微生物群落和炎症因子的影响程度在很大程度上仍未得到探索。在这项研究中,我们收集了 HBV 患者用药前和接受 TDF 治疗的 CHB 患者的粪便样本。

结果

我们评估了 42 名健康受试者(HC 组)、109 名 HBV 感染者,包括 48 名未接受核苷类似物药物治疗的 CHB 患者(No-NAs 组)和 61 名接受 TDF 治疗的 CHB 患者(TDF 组)的肠道微生物群落和炎症因子。16S rRNA 测序显示,TDF 治疗导致 HBV 感染者的肠道微生物群落发生显著变化;然而,HBV 感染者的肠道微生物群落并未完全恢复到先前的失调状态。从 HC 组到 No-NAs 组和 TDF 组,厚壁菌门的相对丰度逐渐降低。梭杆菌门的相对丰度在 No-NAs 组明显高于 HC 组。在属水平上,优势菌属为 Dialister、Eubacterium_hallii_group、Halomonas、Collinsella、Sphingomonas、黄单胞科未分类和根瘤菌科未分类;而 Bacteroides 和 Fusobacterium 的丰度在 No-NAs 和 TDF 组中显著下降。

结论

本研究表明,TDF 治疗显著改善了肠道微生物群落的调节,有助于恢复菌群失调。我们没有观察到血清炎症因子浓度的显著改善,这可能与本研究中 TDF 给药时间相对较短有关。

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