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

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

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

Jianfei Long et al. BMC Microbiol. .

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.

Keywords: Chronic hepatitis B; Dysbiosis; Gut microbiota; Hepatitis; Tenofovir dipivoxil.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

Fig. 1
Fig. 1
Effect of TDF on intestinal flora in patients with CHB. (A) Effect of TDF on alpha diversity of intestinal flora. (B, C) Relative abundances of each bacterial phylum in the patients and healthy controls
Fig. 2
Fig. 2
Gut microbiota differences at the genus level among the three groups. (A) Principal coordinate analysis of β diversity of flora based on Bary-Curits distance (PCoA). (B) LEfSe analysis at genus level
Fig. 3
Fig. 3
Relative abundances of differential genera and potential key taxa responsible for the differences in HC, No-NAs, and TDF groups
Fig. 4
Fig. 4
Correlation between clinical parameters and gut microbiota (A) Correlation between inflammatory factors and gut microbiota. (B) Correlation between microbial genera enriched in the No-NAs and TDF groups. *p-value smaller than 0.05, **p-value smaller than 0.01 and ***p-value smaller than 0.001
Fig. 5
Fig. 5
KEGG pathway analysis of HC, No-NAs, and TDF groups
Fig. 6
Fig. 6
Effect of TDF on intestinal flora in patients with CHB. (A) Effect of TDF on alpha diversity of intestinal flora. (B) Phylum level differences of microbiota. Phase 1 are HBeAg-negative patients and phase 2 are HBeAg-positive patients
Fig. 7
Fig. 7
Characteristics of gut microbiota in patients with hepatitis B and differences in intestinal flora. (A) Principal coordinate analysis of β diversity of flora based on Bary-Curits distance (PCoA). (B) LEfSe analysis at genus level. (C) Relative abundances at the genus level. Phase 1 are HBeAg-negative patients and phase 2 are HBeAg-positive patients

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