ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Intestinal Microbiome
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1565416
This article is part of the Research TopicIntestinal microenvironment and autoimmune diseasesView all 4 articles
Alteration in gut microbiota accompanied by increased intestinal permeability and Tfh/Tfr imbalance in patients with active SLE
Provisionally accepted
- 1Qingdao Municipal Hospital, Qingdao University Medical College, Qingdao, Shandong Province, China
- 2School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong Province, China
- 3Department of Immunology and Rheumatology, Qingdao Municipal Hospital, Qingdao, China
- 4School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong Province, China
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Background: Increased 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. Methods: In 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. Results:Decreased 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. Conclusion: Zonulin may be involved in the Tfh/Tfr immune imbalance in patients with lupusSLE, 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.
Keywords: Gut Microbiota, systemic lupus erythematosus, Zonulin, Tfh/Tfr, IL-2
Received: 23 Jan 2025; Accepted: 12 May 2025.
Copyright: © 2025 Chu, Li, Wang, Guo, Zhao, Han and Xing. 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) or licensor 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.
* Correspondence: Qian Xing, Department of Immunology and Rheumatology, Qingdao Municipal Hospital, Qingdao, China
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