Hepatitis B Virus Infection Alters Gut Microbiota Composition in Mice.

Qingfeng Zhu,Dongliang Yang,Xin Zhou,Bin Zhu,Baoju Wang,Xin Zheng,Xiaoran Li,Panpan Xia,Weina Guo,Junzhong Wang

doi:10.3389/fcimb.2019.00377

Abstract

Gut microbiota composition is known to be associated with the progression of hepatitis B virus (HBV)-related liver cirrhosis in humans, outcome of HBV infection in mice, and seroconversion of HBV e-antigen in nucleot(s)ide analog-treated patients. The dynamic alteration of the gut microbiota following HBV infection is still unknown. In this study, a hydrodynamic injection mouse model mimicking acute or chronic HBV infection in humans with comparable virological and immunological features was used. The composition of gut microbiota in the control mice and mice with acute or chronic HBV infection was analyzed at different time points using the Illumina MiSeq platform. The expression of immune molecules in the colon was detected by real-time polymerase chain reaction. We found that the changes in gut microbiota composition, including the total operational taxonomic unit (OTU) count and Shannon-Weaver index, were significantly delayed in mice with HBV infection. Furthermore, the ratio of Bacteroidetes and Firmicutes was stable in the control mice, whereas remarkable dynamic patterns were observed in mice with HBV infection. Interestingly, the dynamic changes in Lactobacillus and Bifidobacterium were found to differ in acute or chronic HBV infection. In addition, the expression of IFN-γ and PD-L1 in the colon was found to be up-regulated early in mice with acute HBV infection, whereas the expression of PD-L1 in the colon of mice with chronic HBV infection was up-regulated later. These data indicate that HBV infection could hamper the development of the gut microbiota community and dynamically change the gut Firmicutes/Bacteroidetes ratio. These data improve our understanding of the relationship between gut microbiota and HBV infection.

Highlights

A trillion microbial cells colonize the mammalian intestine; these are collectively termed gut microbiota
Consistent with the findings of a previous study, we found that HBV surface antigen (HBsAg), HBV e antigen (HBeAg), and hepatitis B virus (HBV) DNA were detected 1 day after hydrodynamic injection (HI), decreased rapidly, and cleared within 21 days after HI of the pSM2/HBV plasmid in mice
HBV surface antibody (HBsAb) was detected shortly after HBsAg clearance in mice injected with the pSM2/HBV plasmid, while it was consistently undetected in those injected with the pAAV/HBV1.2 plasmid

Summary

Introduction

A trillion microbial cells colonize the mammalian intestine; these are collectively termed gut microbiota. The healthy gut microbiota can be characterized by the richness of the gut ecosystem, its amenability to perturbation, and its ability to return to the pre-perturbation state in terms of its diversity, stability, resistance, and resilience. Gut microbiota dysbiosis is described as a compositional and functional alteration in the gut microbiota that is driven by a set of environment- and host-related factors that perturb the microbial ecosystem to an extent that exceeds its resistance and resilience capabilities (Levy et al, 2017). Previous studies have showed that live commensal bacteria can be sampled by intestinal dendritic cells (DCs) and transferred to the liver via the lymphatic route or portal vein (Rescigno et al, 2001; Macpherson and Uhr, 2004; Fung et al, 2016). The liver can act as a second firewall partially because Kupffer cells can clear commensal bacteria from the systemic vasculature, mirroring their role in pathogen clearance (Balmer et al, 2014)

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Conclusion