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维持性血液透析中的免疫-微生物群失调:基于16S rRNA测序的肠道菌群和T细胞谱分析

Immune-microbiota dysregulation in maintenance hemodialysis: a 16S rRNA sequencing-based analysis of gut flora and T cell profiles.

作者信息

Lv Yan, Yang Xiuting, Sun Xiaowu, Ren Xiaohong

机构信息

Department of Nephrology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China.

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Ren Fail. 2025 Dec;47(1):2498630. doi: 10.1080/0886022X.2025.2498630. Epub 2025 May 15.

DOI:10.1080/0886022X.2025.2498630
PMID:40375064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12082729/
Abstract

BACKGROUND

Maintenance hemodialysis (MHD) patients frequently exhibit immune dysregulation and gut dysbiosis, both of which contribute to increased infection risk and adverse outcomes. However, the relationship between gut microbial composition and immune competence in this population remains underexplored.

METHODS

This study assessed 45 MHD patients and 30 healthy controls, stratifying MHD patients into immunocompetent (HD-NLI, CD4/CD8 ≥ 1) and immunodeficient (HD-LI, CD4/CD8 < 1) groups. Circulating cytokines (IL-6, IL-10, IL-12, TNF-α, IFN-γ) were quantified using ELISA. Gut microbiota profiles were derived 16S rRNA gene sequencing (V3-V4 regions), followed by QIIME2 and LEfSe-based bioinformatics analyses.

RESULTS

HD-LI patients displayed severe T cell dysregulation and elevated pro-inflammatory cytokines. Compared to controls, HD patients had reduced abundance of beneficial taxa (e.g., ), and enrichment of pro-inflammatory taxa (e.g., ). LEfSe identified 39 discriminatory taxa with distinct immune group signatures. Redundancy analysis revealed that CD4 levels, CD4/CD8 ratios, and TNF-α significantly shaped microbiota composition. Correlation analysis confirmed strong associations between immune parameters and microbial taxa involved in short-chain fatty acid (SCFA) metabolism.

CONCLUSION

This study provides novel evidence linking gut microbial dysbiosis to immune impairment in MHD patients. The findings suggest that SCFA-producing bacteria are depleted in immunodeficient states, offering a potential target for microbiota-directed immunomodulatory therapies in ESRD.

摘要

背景

维持性血液透析(MHD)患者经常出现免疫失调和肠道菌群失调,这两者都会增加感染风险和不良后果。然而,该人群中肠道微生物组成与免疫能力之间的关系仍未得到充分探索。

方法

本研究评估了45例MHD患者和30例健康对照,将MHD患者分为免疫功能正常(HD-NLI,CD4/CD8≥1)和免疫缺陷(HD-LI,CD4/CD8<1)组。使用酶联免疫吸附测定法(ELISA)对循环细胞因子(IL-6、IL-10、IL-12、TNF-α、IFN-γ)进行定量。通过16S rRNA基因测序(V3-V4区域)获得肠道微生物群谱,随后进行基于QIIME2和LEfSe的生物信息学分析。

结果

HD-LI患者表现出严重的T细胞失调和促炎细胞因子升高。与对照组相比,HD患者有益类群(如 )的丰度降低,促炎类群(如 )富集。LEfSe鉴定出39个具有不同免疫组特征的鉴别类群。冗余分析表明,CD4水平、CD4/CD8比值和TNF-α显著影响微生物群组成。相关性分析证实免疫参数与参与短链脂肪酸(SCFA)代谢的微生物类群之间存在强关联。

结论

本研究提供了新的证据,将肠道微生物群失调与MHD患者的免疫损伤联系起来。研究结果表明,产生SCFA的细菌在免疫缺陷状态下减少,这为终末期肾病(ESRD)中针对微生物群的免疫调节治疗提供了一个潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed66/12082729/be05498a60c9/IRNF_A_2498630_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed66/12082729/6272cbba7bdb/IRNF_A_2498630_UF0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed66/12082729/582e613a937c/IRNF_A_2498630_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed66/12082729/7b74bde92148/IRNF_A_2498630_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed66/12082729/bc025edb6cb0/IRNF_A_2498630_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed66/12082729/be05498a60c9/IRNF_A_2498630_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed66/12082729/6272cbba7bdb/IRNF_A_2498630_UF0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed66/12082729/582e613a937c/IRNF_A_2498630_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed66/12082729/7b74bde92148/IRNF_A_2498630_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed66/12082729/bc025edb6cb0/IRNF_A_2498630_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed66/12082729/be05498a60c9/IRNF_A_2498630_F0004_C.jpg

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