From Viral Fossils to β-Cell Futures: A Retro-Exposome Framework for Type 1 Diabetes.

Type 1 diabetes affects over 8.4 million individuals worldwide, with approximately 0.5 million new cases annually, and continues to impose substantial morbidity and mortality, particularly in settings where delayed diagnosis is common. Diabetic ketoacidosis occurs at presentation in 20-80% of newly diagnosed children, underscoring persistent gaps in early detection and prevention. Recent evidence linking antibody signatures against human endogenous retroviruses and Mycobacterium avium subspecies paratuberculosis provides a mechanistically provocative perspective on disease pathogenesis. Building on this work, we propose a "retro-exposome-to-β-cell" framework in which microbial exposure and retroelement activation converge to amplify interferon signaling, antigen presentation, and β-cell vulnerability. We highlight the need for cross-population validation, functional studies in β-cell and immune systems, and longitudinal evaluation to determine the causal and predictive relevance of these signatures. Integrating microbial immunology with retroelement biology may offer a pathway toward earlier detection and more equitable prevention strategies in type 1 diabetes.