Modification of Intestinal Microbiota Dysbiosis by Low-Dose Interleukin-2 in Dermatomyositis: A Post Hoc Analysis From a Clinical Trial Study.
Modification of Intestinal Microbiota Dysbiosis by Low-Dose Interleukin-2 in Dermatomyositis: A Post Hoc Analysis From a Clinical Trial Study.
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DOI：
10.3389/fcimb.2022.757099
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发表时间：
2022
影响因子：
5.7
通讯作者：
He J
中科院分区：
文献类型：
--
作者：
Zhufeng Y;Xu J;Miao M;Wang Y;Li Y;Huang B;Guo Y;Tian J;Sun X;Li J;Lu D;Li Z;Li Y;He J
已经观察到微生物群在自身免疫性疾病（包括特发性炎性肌病（IIM））中发生改变，并且与不同的治疗相关。低剂量IL-2治疗成为活动性IIM的新选择。本研究旨在探讨小剂量IL-2对肠内营养不良肠道生态失调的调节作用。在这项研究中，13例活动性IIM患者入组，接受1 ×106 IU IL-2皮下注射，每隔一天一次，持续12周，外加标准治疗。评估临床应答和免疫应答。获得粪便样本以探索靶向16 S rRNA基因的V3-V4区域的粪便微生物群的结构和功能改变，并分析其与临床和免疫学特征的关联。我们的研究表明，与健康对照组相比，IIM患者的微生物群多样性显着下降。与炎症相关的细菌如普雷沃氏菌科增加，而一些丁酸盐产生菌如假丁酸弧菌、毛螺菌科、罗斯拜瑞氏菌属和布劳特氏菌属显著减少。IIM患者中与疾病活动相关的改变。小剂量IL-2治疗后，92.31%（12/13）的患者在第12周达到IMACS DOI。第12周Treg细胞比例较基线显著增加（15.9% [7.73，19.4%] vs. 9.89% [6.02，11.8%]，P = 0.015）。有趣的是，某些产丁酸盐的细菌在IL-2处理后显著增加，如毛螺菌科（Lachnospiraceae）、假丁酸弧菌（Pseudobutyrivibrio）等，并与L-天冬酰胺和L-亮氨酸的升高有关。低剂量IL-2对NOD小鼠肠道微生物群的影响更加明显。总之，所提供的数据表明，低剂量IL-2在活动性IIM中是有效的，并强调了改变微生态失调的肠道微生物组以治疗IIM的潜力。
The microbiota has been observed altered in autoimmune diseases, including idiopathic inflammatory myopathies (IIMs), and associated with different treatments. Low-dose IL-2 treatment emerges as a new option for active IIMs. This study aims to explore the role of low-dose IL-2 in regulating intestinal dysbiosis involved in the IIMs. In this study, 13 patients with active IIMs were enrolled and received 1 ×106 IU of IL-2 subcutaneously every other day for 12 weeks plus standard care. The clinical response and immune response were assessed. Stool samples were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3–V4 region of the 16S rRNA gene and analyze their associations with clinical and immunological characteristics. Our study demonstrated that diversity of microbiota decreased remarkably in patients with IIMs, compared to healthy controls. The inflammatory-related bacteria, such as Prevotellaceae increased, while some butyrate-producing bacteria, such as Pseudobutyrivibrio, Lachnospiraceae, Roseburia, and Blautia, decreased significantly. The alteration associated with disease activities in patients with IIMs. After low-dose IL-2 treatment, 92.31% (12/13) of patients achieved IMACS DOI at week 12. Proportion of Treg cells significantly increased at week 12 compared with that in baseline (15.9% [7.73, 19.4%] vs. 9.89% [6.02, 11.8%], P = 0.015). Interestingly, certain butyrate-producing bacteria increase significantly after IL-2 treatment, like Lachnospiraceae, Pseudobutyrivibrio, etc., and are associated with a rise in L-Asparagine and L-Leucine. The effects of low-dose IL-2 on gut microbiota were more apparent in NOD mice. Together, the data presented demonstrated that low-dose IL-2 was effective in active IIMs and highlighted the potential for modifying the intestinal microbiomes of dysbiosis to treat IIMs.
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影响因子：
16.6
作者：
Jangi S;Gandhi R;Cox LM;Li N;von Glehn F;Yan R;Patel B;Mazzola MA;Liu S;Glanz BL;Cook S;Tankou S;Stuart F;Melo K;Nejad P;Smith K;Topçuolu BD;Holden J;Kivisäkk P;Chitnis T;De Jager PL;Quintana FJ;Gerber GK;Bry L;Weiner HL
通讯作者：
Weiner HL
影响因子：
27.4
作者：
Lundberg IE;Tjärnlund A;Bottai M;Werth VP;Pilkington C;Visser M;Alfredsson L;Amato AA;Barohn RJ;Liang MH;Singh JA;Aggarwal R;Arnardottir S;Chinoy H;Cooper RG;Dankó K;Dimachkie MM;Feldman BM;Torre IG;Gordon P;Hayashi T;Katz JD;Kohsaka H;Lachenbruch PA;Lang BA;Li Y;Oddis CV;Olesinska M;Reed AM;Rutkowska-Sak L;Sanner H;Selva-O'Callaghan A;Song YW;Vencovsky J;Ytterberg SR;Miller FW;Rider LG;International Myositis Classification Criteria Project consortium, The Euromyositis register and The Juvenile Dermatomyositis Cohort Biomarker Study and Repository (JDRG) (UK and Ireland)
通讯作者：
International Myositis Classification Criteria Project consortium, The Euromyositis register and The Juvenile Dermatomyositis Cohort Biomarker Study and Repository (JDRG) (UK and Ireland)
影响因子：
3.8
作者：
Miao M;Li Y;Huang B;Chen J;Jin Y;Shao M;Zhang X;Sun X;He J;Li Z
通讯作者：
Li Z
影响因子：
27.4
作者：
Alpizar-Rodriguez, Deshire;Lesker, Till Robin;Strowig, Till
通讯作者：
Strowig, Till
影响因子：
29
作者：
Mariampillai, Kuberaka;Granger, Benjamin;Benveniste, Olivier
通讯作者：
Benveniste, Olivier