Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response
Background and aimsGiven 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 resp...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1152987/full |
| _version_ | 1797835607891771392 |
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| author | Fengna Yan Qun Zhang Ke Shi Yi Zhang Bingbing Zhu Yufei Bi Xianbo Wang |
| author_facet | Fengna Yan Qun Zhang Ke Shi Yi Zhang Bingbing Zhu Yufei Bi Xianbo Wang |
| author_sort | Fengna Yan |
| collection | DOAJ |
| description | Background and aimsGiven 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.MethodsHere, 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.ResultsWe 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.ConclusionsOur 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. |
| first_indexed | 2024-04-09T14:56:19Z |
| format | Article |
| id | doaj.art-5774a73309bf4d6c9a88f1d54d27b786 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-09T14:56:19Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-5774a73309bf4d6c9a88f1d54d27b7862023-05-02T05:05:00ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-05-011310.3389/fcimb.2023.11529871152987Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune responseFengna YanQun ZhangKe ShiYi ZhangBingbing ZhuYufei BiXianbo WangBackground and aimsGiven 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.MethodsHere, 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.ResultsWe 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.ConclusionsOur 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.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1152987/fullgut microbiomeliver diseaseT cell immunosuppressionhepatocellular carcinomaperipheral immune response |
| spellingShingle | Fengna Yan Qun Zhang Ke Shi Yi Zhang Bingbing Zhu Yufei Bi Xianbo Wang Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response Frontiers in Cellular and Infection Microbiology gut microbiome liver disease T cell immunosuppression hepatocellular carcinoma peripheral 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 | gut microbiome liver disease T cell immunosuppression hepatocellular carcinoma peripheral immune response |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1152987/full |
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