Interindividual variability in food-derived peptide bioavailability and function: peptide metabotypes and responder...

Food-derived bioactive peptides are commonly evaluated as though a standardised protein, hydrolysate, or peptide-containing food produces comparable biological exposure across consumers. Emerging human evidence challenges this assumption because food structure, gastrointestinal physiology, intestinal peptidases, epithelial transport, microbial metabolism, age, metabolic status, medication use, and habitual diet can alter the peptides and metabolites generated after ingestion. This critical review examines interindividual variability as a determinant of food-peptide efficacy and develops a precision-nutrition framework linking product composition to digestive peptide profiles and physiological response. We synthesise evidence from human digestion studies, jejunal peptidomics, transport and metabolism models, microbiome research, peptide pharmacokinetics, and clinical interventions involving antihypertensive lactotripeptides, dipeptidyl peptidase-IV (DPP-IV)-inhibitory hydrolysates, and collagen peptides. We propose two testable concepts: the peptide metabotype, defined as an individual's reproducible time-resolved profile of food-derived peptides and metabolites after a standardised challenge, and the peptide responder phenotype, defined as the corresponding exposure-response pattern. We outline a core design comprising a characterised product, an appropriate comparator, repeated measurements, a targeted exposure panel and a prespecified physiological endpoint, with additional host profiling guided by the mechanism. This perspective shifts peptide research from universal bioactivity claims toward identifying when, where, and in whom peptide-containing foods are most likely to produce meaningful physiological effects and offers a testable approach to improving reproducibility and evaluating translational relevance.