AGE-RELATED GUT DYSBIOSIS ACCELERATES THYMIC INVOLUTION AND ALTERS PERIPHERAL T CELL REPERTOIRE IN DUCHENNE MUSCULAR DYSTROPHY

Emerging researches highlight a significant interplay between the immune system and skeletal muscle, particularly in the context of inflammatory muscle disorders and dystrophic conditions like Duchenne Muscular Dystrophy (DMD), as well as during the natural process of muscle regeneration. Conventionally, immune system activation was regarded as a consequence of muscle atrophy. However, recent findings have unveiled a malfunction in central tolerance due to thymus alterations and the presence of autoreactive T-lymphocytes in patients with DMD. Moreover, the development and equilibrium of both innate and adaptive immune systems have become increasingly linked to the microbiota, the microorganisms inhabiting the gut. For this purpose, we investigated the role of the commensal microbiota in exacerbating muscle damage via immune system activation. We created a network of expertise to characterize the intestinal environment and its microbial ecology in murine models of muscular dystrophies and we proposed that alterations of commensal communities actively contribute to disease pathogenesis by a combination of adaptive and innate pathways. We also investigated whether healthy and dystrophic aging lead to the proliferation of pathobionts or protective taxa, as well as microorganisms contributing to muscle degeneration and inflammation. Overall, this study provide valuable insights into how the intestinal microbiota shapes the inflammatory response, thereby conferring distinct susceptibility to muscle pathology. Furthermore, we potentially identified novel biomarkers associated with gastrointestinal involvement and disease progression prediction, which could be translated into human studies and aid in stratifying patients based on the most appropriate treatments.