Alteration in gut microbiota accompanied by increased intestinal permeability and Tfh/Tfr imbalance in patients with active SLE

BackgroundIncreased intestinal permeability and altered intestinal microbiota may influence cytokine regulatory immunity in systemic lupus erythematosus (SLE). This study aimed to elucidate the relationship between intestinal flora alters and follicular helper T cells (Tfh), regulatory T cells (Treg...

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Main Authors: Xiaodi Chu, Shuya Li, Yueying Wang, Dazhen Guo, Nana Zhao, Yuanyuan Han, Qian Xing
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1565416/full
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author Xiaodi Chu
Shuya Li
Yueying Wang
Dazhen Guo
Nana Zhao
Yuanyuan Han
Qian Xing
author_facet Xiaodi Chu
Shuya Li
Yueying Wang
Dazhen Guo
Nana Zhao
Yuanyuan Han
Qian Xing
author_sort Xiaodi Chu
collection DOAJ
description BackgroundIncreased intestinal permeability and altered intestinal microbiota may influence cytokine regulatory immunity in systemic lupus erythematosus (SLE). This study aimed to elucidate the relationship between intestinal flora alters and follicular helper T cells (Tfh), regulatory T cells (Treg) cells, and cytokines in SLE.MethodsIn total, 23 patients with active SLE (SLE-A group), 18 patients with stable SLE (SLE-nA group), and 24 healthy controls (HC group) were enrolled. Tfh, follicular T regulatory (Tfr), and Treg cells were measured by flow cytometry, and fecal samples were analyzed using 16S rRNA gene sequencing. The relationship between the gut microbiome and the SLE disease activity index (SLEDAI-2k), zonulin (an indicator of intestinal permeability), IL-2, IL-6, and IL-21 levels was analyzed.ResultsDecreased Treg cells and imbalanced Tfh/Tfr were associated with elevated disease activity in SLE-A group. The increase in zonulin levels in SLE-A group indicated worsened intestinal mucosal barrier damage, potentially linked with the increase in the dominant microflora Escherichia-Shigella. Furthermore, the increase in zonulin was correlated with a severe imbalance in Tfh/Tfr. Moreover, decreased IL-2 levels were associated with a decrease in Ruminococcus and may modulate the reduction in Treg cells during disease progression. Zonulin also exhibited a negative correlation with IL-2.ConclusionZonulin may be involved in the Tfh/Tfr immune imbalance in patients with SLE, and Faecalibacterium and Ruminococcus may contribute to disease development by regulating Treg cells and Tfh/Tfr imbalance. Taken together, these findings may provide new insights into the role of cytokines in the treatment of SLE.
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spelling doaj-art-eba70c9e1a554c5781a69a43f7660d962025-08-20T03:21:50ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-05-011510.3389/fcimb.2025.15654161565416Alteration in gut microbiota accompanied by increased intestinal permeability and Tfh/Tfr imbalance in patients with active SLEXiaodi Chu0Shuya Li1Yueying Wang2Dazhen Guo3Nana Zhao4Yuanyuan Han5Qian Xing6Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong, ChinaSchool of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, ChinaDepartment of Immunology and Rheumatology, Qingdao Municipal Hospital, Qingdao, Shandong, ChinaSchool of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, ChinaSchool of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, ChinaDepartment of Immunology and Rheumatology, Qingdao Municipal Hospital, Qingdao, Shandong, ChinaBackgroundIncreased intestinal permeability and altered intestinal microbiota may influence cytokine regulatory immunity in systemic lupus erythematosus (SLE). This study aimed to elucidate the relationship between intestinal flora alters and follicular helper T cells (Tfh), regulatory T cells (Treg) cells, and cytokines in SLE.MethodsIn total, 23 patients with active SLE (SLE-A group), 18 patients with stable SLE (SLE-nA group), and 24 healthy controls (HC group) were enrolled. Tfh, follicular T regulatory (Tfr), and Treg cells were measured by flow cytometry, and fecal samples were analyzed using 16S rRNA gene sequencing. The relationship between the gut microbiome and the SLE disease activity index (SLEDAI-2k), zonulin (an indicator of intestinal permeability), IL-2, IL-6, and IL-21 levels was analyzed.ResultsDecreased Treg cells and imbalanced Tfh/Tfr were associated with elevated disease activity in SLE-A group. The increase in zonulin levels in SLE-A group indicated worsened intestinal mucosal barrier damage, potentially linked with the increase in the dominant microflora Escherichia-Shigella. Furthermore, the increase in zonulin was correlated with a severe imbalance in Tfh/Tfr. Moreover, decreased IL-2 levels were associated with a decrease in Ruminococcus and may modulate the reduction in Treg cells during disease progression. Zonulin also exhibited a negative correlation with IL-2.ConclusionZonulin may be involved in the Tfh/Tfr immune imbalance in patients with SLE, and Faecalibacterium and Ruminococcus may contribute to disease development by regulating Treg cells and Tfh/Tfr imbalance. Taken together, these findings may provide new insights into the role of cytokines in the treatment of SLE.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1565416/fullgut microbiotasystemic lupus erythematosuszonulinTfh/TfrIL-2
spellingShingle Xiaodi Chu
Shuya Li
Yueying Wang
Dazhen Guo
Nana Zhao
Yuanyuan Han
Qian Xing
Alteration in gut microbiota accompanied by increased intestinal permeability and Tfh/Tfr imbalance in patients with active SLE
Frontiers in Cellular and Infection Microbiology
gut microbiota
systemic lupus erythematosus
zonulin
Tfh/Tfr
IL-2
title Alteration in gut microbiota accompanied by increased intestinal permeability and Tfh/Tfr imbalance in patients with active SLE
title_full Alteration in gut microbiota accompanied by increased intestinal permeability and Tfh/Tfr imbalance in patients with active SLE
title_fullStr Alteration in gut microbiota accompanied by increased intestinal permeability and Tfh/Tfr imbalance in patients with active SLE
title_full_unstemmed Alteration in gut microbiota accompanied by increased intestinal permeability and Tfh/Tfr imbalance in patients with active SLE
title_short Alteration in gut microbiota accompanied by increased intestinal permeability and Tfh/Tfr imbalance in patients with active SLE
title_sort alteration in gut microbiota accompanied by increased intestinal permeability and tfh tfr imbalance in patients with active sle
topic gut microbiota
systemic lupus erythematosus
zonulin
Tfh/Tfr
IL-2
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1565416/full
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