Non-host factors influencing onset and severity of celiac disease

Celiac Disease (CeD) is a chronic autoimmune condition driven by gluten ingestion in genetically predisposed individuals, resulting in inflammatory lesions in the proximal small intestine. While the presence of specific human leukocyte antigen (HLA) linked haplotypes and gluten consumption are necessary for disease development, they alone do not account for the variable onset of CeD in susceptible individuals. This review explores the multifaceted role of non-host factors in CeD development, including dietary and microbial influences. We discuss clinical associations and observations highlighting the impact of these factors on disease onset and severity. Furthermore, we discuss studies in CeD-relevant animal models that offer mechanistic insights into how diet, the microbiome, and enteric infections modulate CeD pathogenesis. Finally, we address the clinical implications and therapeutic potential of understanding these cofactors, offering a promising avenue for preventive and therapeutic interventions in CeD management.