AUTHOR=Yan Fengna , Zhang Qun , Shi Ke , Zhang Yi , Zhu Bingbing , Bi Yufei , Wang Xianbo 

TITLE=Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1152987

DOI=10.3389/fcimb.2023.1152987

ISSN=2235-2988

ABSTRACT=ABSTRACT 
Background and aims: Given hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) exhibits unique gut microbiota characteristics and a significant immunosuppressive tumor microenvironment. Thus, a better understanding of the correlation between gut microbiota and the immunosuppressive response may help predict occurrence and prognosis of HBV-HCC. 
Methods: Ninety clinical samples (healthy control n=30, HBV-cirrhosis n=30, HBV-HCC n=30) were studied. We used the 16S rRNA gene sequencing and flow cytometry to characterize gut microbiota and peripheral immune response of HBV related chronic liver disease (HBV-CLD) patients. Correlation between the gut microbiome and clinical parameters as well as between the gut microbiome and the peripheral immune response of participants was assessed. 
Results: Compared with the healthy group, the abundance of Firmicutes and Bacteroidota was significantly decreased in HBV-CLD patients, yet Proteobacteria and Actinobacteriota were elevated. Diversity of the gut microbiome was reduced as the disease progressesand. The immunosuppressive response of HBV-HCC patients was stronger compared with HBV-cirrhosis (HBV-LC) patients. Furthermore, The percentage of CD3+T, CD4+T and CD8+T cells were positively correlated with the abundance of Bacteroidota, Deferribacterota, and Akkermaniacaeae. The percentage of Treg cell and programmed cell death 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), immune receptor tyrosine based inhibitor motor (ITIM) domain (TIGIT), T-cell immune domain, and multiple domain 3 (TIM-3) in HBV-HCC patients were positively correlated with harmful bacteria, such as Actinobaciota, Myxococota, Streptococcaceae and Eubacterium coprostanoligenes. 
Conclusions: Our study indicated that the dysbiosis of microbiota was associated with the peripheral T cell immune response in HBV-CLD patients.
Keywords: Gut microbiome, liver disease, T cell immunosuppression