Effect of Tenofovir on gut microbiota and inflammatory factors in HBV-infected individuals

Studies have found dysbiosis of the gut microbiota in hepatitis B virus (HBV)-infected individuals. At present, Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs for the treatment of chronic hepatitis B (CHB), but the effect of TDF on gut microbiota and inflammatory factors in CHB patients remains unexplored. In this study, we prospectively collected stool samples from unmedicated HBV patients and CHB patients treated with TDF. Gut microbiota and inflammatory factors were studied in 42 healthy subjects (HC group), 109 HBV-infected individuals, including 48 CHB patients who did not take nucleoside (acid) analogues drugs (No-NAs group) and 61 CHB patients who took TDF (TDF group). 16S rRNA sequencing revealed that TDF treatment can cause significant alterations in intestinal microbiota in HBV-infected individuals, however, HBV-infected individuals cannot fully recover from intestinal microbiota dysbiosis. The phyla of Firmicutes, Proteobacteria, Actinobacteria, and Fusobacteria, are more abundant in No-NAs and TDF groups than in the health controls. The relative abundances of Fusobacteria were significantly higher in the No-NAs group than those in the health controls. The relative abundance of Bacteroidetes in HC, No-NAs, and TDF gradually decreased. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were found to be overrepresented in No-NAs and TDF groups. The abundances of Bacteroides and Fusobacterium were significantly decreased in No-NAs and TDF groups, but there was no significant difference between No-NAs and TDF groups. This study showed that TDF treatment did not completely restore dysregulated gut microbiota and did not reduce the level of serum inflammatory factors effectively. Since the disturbance of gut microbiota is associated with the increase in inflammatory factors, we speculated that the therapeutic effect of TDF may be improved by modulating intestinal microbiota.