BioProject

Gut microbiota (GM) dysbiosis is associated with inflammatory bowel diseases and also with cardiometabolic, neurologic, and autoimmune diseases. More...

Gut microbiota (GM) dysbiosis is associated with inflammatory bowel diseases and also with cardiometabolic, neurologic, and autoimmune diseases. GM composition has a direct effect on the immune system, and vice versa, and particularly on regulatory T cell (Treg) homeostasis. Low-dose interleukin-2 (IL-2LD) stimulates Tregs and is a promising treatment for autoimmune and inflammatory diseases. We aimed to evaluate the impacts of IL-2LD on GM, and correlatively on the immune system. We used 16S ribosomal RNA profiling and metagenomics to characterise GM of mice and humans treated or not with IL-2LD. We performed fecal microbiota transplantation (FMT) from IL-2LD-treated to naive recipient mice and evaluated its effects in models of type-1 diabetes and gut inflammation. IL-2LD markedly affects GM composition in mice and humans. Transfer of an IL-2-tuned microbiota by FMT prevented type 1 diabetes in NOD mice and protected C57BL/6J mice from dextran sulfate sodium-induced colitis. Metagenomic analyses highlighted a role for several species impacted by IL-2LD and for gut microbial pathways involved in the biosynthesis of amino acids, short-chain fatty acids, and L-arginine. Our results demonstrate that IL-2LD induces changes in GM that are involved in the therapeutic effects of IL-2LD and suggest cross-talk between Tregs and GM. These results provide novel perspectives for understanding the mode of action of Treg-directed therapies. Less...