肠道微生物失调与乙型肝炎病毒肝病及与免疫反应的关联。

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

机构信息

Center for Integrative Medicine, Beijing Ditan Hospital Capital Medical University, Beijing, China.

出版信息

Front Cell Infect Microbiol. 2023 May 2;13:1152987. doi: 10.3389/fcimb.2023.1152987. eCollection 2023.

DOI:10.3389/fcimb.2023.1152987

PMID:37201112

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10185817/

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

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 associated with inflammation were enriched. The beneficial bacteria of 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 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 and .

CONCLUSIONS

Our study indicated that gut beneficial bacteria, mainly and 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.

摘要

背景和目的

鉴于乙型肝炎病毒（HBV）相关肝细胞癌（HBV-HCC）表现出独特的肠道微生物群特征和显著的免疫抑制肿瘤微环境。因此，更好地了解肠道微生物群与免疫抑制反应之间的相关性可能有助于预测 HBV-HCC 的发生和预后。

方法

在这里，在一项包含 90 名成年人（健康对照组 n=30、HBV 肝硬化 n=30、HBV-HCC n=30）的临床数据的队列中，进行粪便 16S rRNA 基因测序，并通过流式细胞术分析进行匹配的外周血免疫反应。评估 HBV-HCC 患者肠道微生物组与临床参数以及外周免疫反应之间的显著差异相关性。

结果

我们发现 HBV-CLD 患者的肠道微生物群落结构和多样性变得更加不平衡。与炎症相关的差异微生物群分析得到了富集。有益菌的数量减少了。肠道微生物群的功能分析显示，HBV-CLD 患者的脂多糖生物合成、脂质代谢和丁酸盐代谢显著升高。Spearman 相关性分析显示，与 CD3+T、CD4+T 和 CD8+T 细胞计数呈正相关，而与肝功能障碍呈负相关。此外，配对的外周血显示 CD3+T、CD4+T 和 CD8+T 细胞比例降低，而 T（调节性 T）细胞增加。CD8+T 细胞程序性细胞死亡 1（PD-1）、细胞毒性 T 淋巴细胞抗原 4（CTLA-4）、免疫受体酪氨酸基抑制基序（ITIM）域（TIGIT）、T 细胞免疫结构域和多个结构域 3（TIM-3）的免疫抑制反应在 HBV-HCC 患者中更高。它们与有害细菌呈正相关，如和。