Marine-Derived Proteins: Individual Variability in Health Effects Across Protein Structure, Host Genetics, and Gut Microbiota.

Marine-derived proteins are increasingly used in nutritional interventions, but their health effects show substantial interindividual variability, challenging one-size-fits-all approaches. This review proposes a framework based on a triadic interaction model to explain personalized physiological responses to marine proteins. It considers three main determinants. First, the structural characteristics of marine proteins, such as higher order structure, surface charge, solubility, and processing-induced modifications (e.g., enzymatic hydrolysis, heating), shape their digestion behavior and the profile of bioactive products. Second, host genetic and physiological factors, including variation in digestive enzyme gene copy number, polymorphisms in peptide transporters and metabolic enzymes, and differences in intestinal immune receptors, affect protein digestion, absorption, and immune responses. Third, for protein fractions escaping host upper gastrointestinal digestion, the gut microbiota's compositional and functional features, including community structure and enzyme repertoires, influence downstream colonic fermentation and the generation of microbial metabolites. By integrating these three dimensions, the model links marine protein characteristics with host and microbial factors to clarify mechanisms underlying individual variability in personalized health outcomes and to support the development of more targeted marine protein-based nutritional strategies.