Integrated multi-omics reveals persistent extracellular matrix remodeling in chronic duck footpad dermatitis

Footpad dermatitis (FPD) is a common welfare and production problem in intensively reared poultry, yet the mechanisms responsible for its chronic progression remain poorly understood. To investigate the biological changes associated with chronic FPD, healthy and FPD-affected ducks (Health and FPD groups) were compared using histopathology, transcriptomics, proteomics, microbiome profiling, and metabolomics, with 3-8 biological replicates per group depending on the analytical platform. Histological examination demonstrated marked extracellular matrix (ECM) remodeling, characterized by collagen disorganization, an altered type I/type III collagen ratio, and disrupted matrix organization. Transcriptomic and proteomic analyses consistently identified alterations in ECM-receptor interaction, focal adhesion, and integrin β1/TGF-β-related signaling pathways, showing host molecular alterations associated with persistent ECM remodeling. FPD was also accompanied by marked alterations in both skin and gut microbial communities together with widespread metabolic alterations. Correlation analysis further identified associations among differential microbial taxa, metabolites, and ECM-related genes and proteins. Collectively, these findings indicate that chronic FPD is characterized by persistent extracellular matrix remodeling accompanied by extensive host molecular, microbial, and metabolic alterations. This study extends the current understanding of chronic FPD and provides a foundation for future studies aimed at improving footpad health, animal welfare, and production sustainability in poultry.