Abstract
Dysbiosis of gut microbiota during the progression of HBV-related liver disease is not well understood, as there are very few reports that discuss the featured bacterial taxa in different stages. The aim of this study was to reveal the featured bacterial species whose abundances are directly associated with HBV disease progression, that is, progression from healthy subjects to, chronic HBV infection, chronic hepatitis B to liver cirrhosis. Approximately 400 fecal samples were collected, and 97 samples were subjected to 16S rRNA gene sequencing after age and BMI matching. Compared with the healthy individuals, significant gut microbiota alterations were associated with the progression of liver disease. LEfSe results showed that the HBV infected patients had higher Fusobacteria, Veillonella, and Haemophilus abundance while the healthy individuals had higher levels of Prevotella and Phascolarctobacterium. Indicator analysis revealed that 57 OTUs changed as the disease progressed, and their combination produced an AUC value of 90% (95% CI: 86–94%) between the LC and non-LC groups. In addition, the abundances of OTU51 (Dialister succinatiphilus) and OTU50 (Alistipes onderdonkii) decreased as the disease progressed, and these results were further verified by qPCR. The LC patients had the higher bacterial network complexity, which was accompanied with a lower abundance of potential beneficial bacterial taxa, such as Dialister and Alistipes, while they had a higher abundance of pathogenic species within Actinobacteria. The compositional and network changes in the gut microbiota in varied CHB stages, suggest the potential contributions of gut microbiota in CHB disease progression.
Highlights
Hepatitis B virus (HBV) infection is a global epidemic public health issue (3.5% of the global population have been infected), which may be accompanied by ongoing low-grade liver inflammation (Lavanchy et al, 2004; Ott et al, 2012)
Previous studies indicate that compositional changes of the gut microbiota are closely related to chronic liver diseases, such as non-alcoholic fatty liver disease (NAFLD) (Bibbò et al, 2018; Hoyles et al, 2018; Ponziani et al, 2018), non-alcoholic steatohepatitis (NASH) (Yamada et al, 2017; Bomhof et al, 2018; Ye et al, 2018), alcoholic liver disease (ALD) (Hartmann et al, 2018; Shao et al, 2018; Stärkel et al, 2018), hepatic encephalopathy (HE) (Tilg et al, 2016; Mancini et al, 2018), cirrhosis (Garcia-Tsao and Wiest, 2004; Bajaj et al, 2018a; Guo et al, 2018), hepatocellular carcinoma (HCC) (Zamparelli et al, 2017), and HBV infection
Based on the above consideration, our study focused on the gut microbiota of 21 healthy individuals and 76 chronic HBV infected patients with HBV infection (HBVI), chronic hepatitis B (CHB), or liver cirrhosis (LC) through high throughput 16S ribosomal RNA (rRNA) gene sequencing
Summary
Hepatitis B virus (HBV) infection is a global epidemic public health issue (3.5% of the global population have been infected), which may be accompanied by ongoing low-grade liver inflammation (Lavanchy et al, 2004; Ott et al, 2012). Previous studies indicate that compositional changes of the gut microbiota are closely related to chronic liver diseases, such as non-alcoholic fatty liver disease (NAFLD) (Bibbò et al, 2018; Hoyles et al, 2018; Ponziani et al, 2018), non-alcoholic steatohepatitis (NASH) (Yamada et al, 2017; Bomhof et al, 2018; Ye et al, 2018), alcoholic liver disease (ALD) (Hartmann et al, 2018; Shao et al, 2018; Stärkel et al, 2018), hepatic encephalopathy (HE) (Tilg et al, 2016; Mancini et al, 2018), cirrhosis (Garcia-Tsao and Wiest, 2004; Bajaj et al, 2018a; Guo et al, 2018), hepatocellular carcinoma (HCC) (Zamparelli et al, 2017), and HBV infection. The systematic monitoring of HBV infected patients to reveal unique bacterial taxa that can postpone disease course during severe hepatic deterioration, is of great importance
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