Eggshell membrane-derived bioactives for functional foods: gastrointestinal fate, intestinal interactions, and systemic health implications

Eggshell membrane (ESM) is a protein- and glycosaminoglycan-rich food by-product with growing potential as a source of functional ingredients. However, the biological relevance of orally consumed ESM depends not only on its initial composition, but also on how processing and gastrointestinal transit reshape the molecular forms presented to the host. This review integrates current evidence on ESM composition and processing with its gastrointestinal fate, intestinal interactions, and downstream health implications. Micronization, enzymatic hydrolysis, fermentation, and combined treatments generate products that differ in solubility, molecular-weight distribution, peptide sequence, and glycosaminoglycan accessibility, thereby establishing distinct digestive starting states. Gastrointestinal digestion further produces heterogeneous pools of soluble peptides, incompletely hydrolyzed proteins, and digestion-resistant fractions. At the intestinal interface, selected ESM-derived components can modulate epithelial barrier properties, redox homeostasis, inflammatory signaling, and molecular targets such as DPP-IV, whereas resistant fractions reaching the distal intestine are associated with context-dependent microbiota remodeling and changes in metabolites including butyrate and branched-chain fatty acids. Although joint, skin, bone, and other systemic benefits have been reported, direct causal links between post-digestion ESM structures, intestinal mechanisms, and systemic outcomes remain limited. Future studies integrating standardized digestion, peptidomics, metabolomics, transport analysis, and isotope tracing are needed to establish structure-processing-gastrointestinal fate-function relationships.