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

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 re...

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Autores principales: Yan, Fengna, Zhang, Qun, Shi, Ke, Zhang, Yi, Zhu, Bingbing, Bi, Yufei, Wang, Xianbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185817/
https://www.ncbi.nlm.nih.gov/pubmed/37201112
http://dx.doi.org/10.3389/fcimb.2023.1152987
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author Yan, Fengna
Zhang, Qun
Shi, Ke
Zhang, Yi
Zhu, Bingbing
Bi, Yufei
Wang, Xianbo
author_facet Yan, Fengna
Zhang, Qun
Shi, Ke
Zhang, Yi
Zhu, Bingbing
Bi, Yufei
Wang, Xianbo
author_sort Yan, Fengna
collection PubMed
description 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: Here, in a cohort of ninety adults (healthy control n=30, HBV-cirrhosis n=30, HBV-HCC n=30) with clinical data, fecal 16S rRNA gene sequencing, matched peripheral blood immune response with flow cytometry analysis. Correlation between the gut microbiome of significantly different in HBV-HCC patients and clinical parameters as well as the peripheral immune response was assessed. RESULTS: We found that community structures and diversity of the gut microbiota in HBV-CLD patients become more unbalanced. Differential microbiota analysis that p:Acidobacteriota, p:Proteobacteria, p:Campilobacterota, f:Streptococcaceae, g:Klebsiella associated with inflammation were enriched. The beneficial bacteria of f:Clostridia UCG−014, f:Oscillospiraceae, f:_Rikenellaceae, g:_Barnesiella, g:Prevotella, g:Agathobacter were decreased. Functional analysis of gut microbiota revealed that lipopolysaccharide biosynthesis, lipid metabolism, butanoate metabolism were significantly elevated in HBV-CLD patients. Spearman’s correlation analysis showed that Muribaculaceae, Akkermaniacaeae, [Eubacterium]_coprostanoligenes_group, RF39, Tannerellaceae have positive correlation with CD3+T, CD4+T and CD8+T cell counts while negatively correlated with liver dysfunction. Furthermore, paired peripheral blood showed a decreased proportion of CD3+T, CD4+T and CD8+T cells, while an increased T (Treg) cells. The immunosuppressive response of 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) of CD8+T cells were higher in HBV-HCC patients. They were positively correlated with harmful bacteria, such as Actinobaciota, Myxococota, Streptococcaceae and Eubacterium coprostanoligenes. CONCLUSIONS: Our study indicated that gut beneficial bacteria, mainly Firmicutes and Bacteroides appeared dysbiosis in HBV-CLD patients. They have negative regulation of liver dysfunction and T cell immune response. It provides potential avenues for microbiome-based prevention and intervention for anti-tumor immune effects of HBV-CLD.
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spelling pubmed-101858172023-05-17 Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response Yan, Fengna Zhang, Qun Shi, Ke Zhang, Yi Zhu, Bingbing Bi, Yufei Wang, Xianbo Front Cell Infect Microbiol Cellular and Infection Microbiology 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: Here, in a cohort of ninety adults (healthy control n=30, HBV-cirrhosis n=30, HBV-HCC n=30) with clinical data, fecal 16S rRNA gene sequencing, matched peripheral blood immune response with flow cytometry analysis. Correlation between the gut microbiome of significantly different in HBV-HCC patients and clinical parameters as well as the peripheral immune response was assessed. RESULTS: We found that community structures and diversity of the gut microbiota in HBV-CLD patients become more unbalanced. Differential microbiota analysis that p:Acidobacteriota, p:Proteobacteria, p:Campilobacterota, f:Streptococcaceae, g:Klebsiella associated with inflammation were enriched. The beneficial bacteria of f:Clostridia UCG−014, f:Oscillospiraceae, f:_Rikenellaceae, g:_Barnesiella, g:Prevotella, g:Agathobacter were decreased. Functional analysis of gut microbiota revealed that lipopolysaccharide biosynthesis, lipid metabolism, butanoate metabolism were significantly elevated in HBV-CLD patients. Spearman’s correlation analysis showed that Muribaculaceae, Akkermaniacaeae, [Eubacterium]_coprostanoligenes_group, RF39, Tannerellaceae have positive correlation with CD3+T, CD4+T and CD8+T cell counts while negatively correlated with liver dysfunction. Furthermore, paired peripheral blood showed a decreased proportion of CD3+T, CD4+T and CD8+T cells, while an increased T (Treg) cells. The immunosuppressive response of 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) of CD8+T cells were higher in HBV-HCC patients. They were positively correlated with harmful bacteria, such as Actinobaciota, Myxococota, Streptococcaceae and Eubacterium coprostanoligenes. CONCLUSIONS: Our study indicated that gut beneficial bacteria, mainly Firmicutes and Bacteroides appeared dysbiosis in HBV-CLD patients. They have negative regulation of liver dysfunction and T cell immune response. It provides potential avenues for microbiome-based prevention and intervention for anti-tumor immune effects of HBV-CLD. Frontiers Media S.A. 2023-05-02 /pmc/articles/PMC10185817/ /pubmed/37201112 http://dx.doi.org/10.3389/fcimb.2023.1152987 Text en Copyright © 2023 Yan, Zhang, Shi, Zhang, Zhu, Bi and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Yan, Fengna
Zhang, Qun
Shi, Ke
Zhang, Yi
Zhu, Bingbing
Bi, Yufei
Wang, Xianbo
Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response
title Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response
title_full Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response
title_fullStr Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response
title_full_unstemmed Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response
title_short Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response
title_sort gut microbiota dysbiosis with hepatitis b virus liver disease and association with immune response
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185817/
https://www.ncbi.nlm.nih.gov/pubmed/37201112
http://dx.doi.org/10.3389/fcimb.2023.1152987
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