MicroRNAs as a potential missing link between environment and type 1 diabetes development

Abstract

The pathogenesis of type 1 diabetes (T1D) is multifactorial and remains incompletely understood. Although genetic susceptibility plays a major role, epidemiological evidence indicates an important contribution of non-genetic factors. Viral infections, dietary factors, alterations in gut microbiota, pollutants and early-life exposures have all been associated with T1D risk, but the molecular mechanisms linking these exposures to disease development remain unclear. MicroRNA dysregulation has been reported in T1D and is associated with immune regulation, pancreatic β-cell function, insulin secretion and cell survival. At the same time, environmental and early-life exposures can alter microRNA expression. These two lines of evidence raise the hypothesis that environmentally responsive microRNAs may represent molecular points of convergence between environmental influences and pathways relevant to T1D. In this narrative review, we examine evidence linking environmental and early-life exposures to microRNA alterations and evaluate the potential relevance of these changes to T1D-related immune and β-cell pathways. Across human studies and T1D-relevant experimental models, environmental and early-life exposures have been associated with alterations in microRNA expression, with several microRNAs recurring across distinct environmental contexts. Among these, miR-155, miR-146a and miR-375 emerge as candidate convergent regulatory nodes linking environmental responses with immune and β-cell pathways relevant to T1D. However, direct evidence that environmentally induced alterations in these microRNAs mediate T1D development in humans is still lacking. These findings may also have clinical relevance. Circulating microRNA signatures could complement existing biomarkers in T1D, but consistent analytical methods and replication in independent cohorts are still needed before routine use. Therapeutic targeting of microRNAs remains experimental. Overall, the reviewed evidence points to environmentally responsive microRNAs as candidate molecular links between environmental exposures and immune and β-cell pathways relevant to T1D, although a causal role in disease development has not been established.