Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Stem Cell Research Center, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Front Cell Infect Microbiol. 2024 Mar 12;14:1349397. doi: 10.3389/fcimb.2024.1349397. eCollection 2024.
Graves' disease (GD), characterized by immune aberration, is associated with gut dysbiosis. Despite the growing interest, substantial evidence detailing the precise impact of gut microbiota on GD's autoimmune processes remains exceedingly rare.
This study was designed to investigate the influence of gut microbiota on immune dysregulation in GD.
It encompassed 52 GD patients and 45 healthy controls (HCs), employing flow cytometry and enzyme-linked immunosorbent assay to examine lymphocyte and cytokine profiles, alongside lipopolysaccharide (LPS) levels. Gut microbiota profiles and metabolic features were assessed using 16S rRNA gene sequencing and targeted metabolomics.
Our observations revealed a disturbed B-cell distribution and elevated LPS and pro-inflammatory cytokines in GD patients compared to HCs. Significant differences in gut microbiota composition and a marked deficit in short-chain fatty acid (SCFA)-producing bacteria, including ASV263(), ASV1451(), and ASV503(), were observed in GD patients. These specific bacteria and SCFAs showed correlations with thyroid autoantibodies, B-cell subsets, and cytokine levels. In vitro studies further showed that LPS notably caused B-cell subsets imbalance, reducing conventional memory B cells while increasing naïve B cells. Additionally, acetate combined with propionate and butyrate showcased immunoregulatory functions, diminishing cytokine production in LPS-stimulated cells.
Overall, our results highlight the role of gut dysbiosis in contributing to immune dysregulation in GD by affecting lymphocyte status and cytokine production.
Graves 病（GD）以免疫异常为特征，与肠道菌群失调有关。尽管人们越来越关注，但详细描述肠道微生物群对 GD 自身免疫过程的确切影响的证据仍然非常罕见。
本研究旨在探讨肠道微生物群对 GD 免疫失调的影响。
纳入 52 例 GD 患者和 45 例健康对照者（HCs），采用流式细胞术和酶联免疫吸附试验检测淋巴细胞和细胞因子谱，以及脂多糖（LPS）水平。采用 16S rRNA 基因测序和靶向代谢组学评估肠道微生物群谱和代谢特征。
与 HCs 相比，GD 患者表现出 B 细胞分布紊乱、LPS 和促炎细胞因子水平升高。GD 患者的肠道微生物群组成存在显著差异，短链脂肪酸（SCFA）产生菌，包括 ASV263()、ASV1451()和 ASV503()明显减少。这些特定的细菌和 SCFAs 与甲状腺自身抗体、B 细胞亚群和细胞因子水平相关。体外研究进一步表明，LPS 显著导致 B 细胞亚群失衡，减少常规记忆 B 细胞，增加幼稚 B 细胞。此外，醋酸盐与丙酸盐和丁酸盐联合具有免疫调节功能，减少 LPS 刺激细胞中细胞因子的产生。
总的来说，我们的研究结果强调了肠道菌群失调通过影响淋巴细胞状态和细胞因子产生在 GD 免疫失调中的作用。
