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.