Fermented Foods from a Functional Foods Perspective: Mechanistic Pathways, Bioactive Systems, and Effects on Human Health

Fermentation is among the oldest food technologies, yet its relevance now extends well beyond preservation. Fermented foods are increasingly viewed as matrix-dependent biological systems whose microbial and chemical composition evolves during fermentation and post-fermentation processing, and whose functional components may undergo further transformation during gastrointestinal digestion and host–microbiome interaction, rather than as passive carriers of single nutrients or microorganisms. This review synthesizes mechanistic, compositional, and clinical evidence on fermented foods as functional foods through three core scientific pillars: (i) the biological and matrix-related determinants of functionality, including microbial genotype and community ecology, enzymatic transformation, matrix restructuring, fermentation and post-fermentation processing, gastrointestinal digestion, and host phenotype; (ii) the principal fermentation-derived bioactive systems, including bioactive peptides, exopolysaccharides, organic acids, microbially synthesized vitamins, bioaccessible minerals, biotransformed phenolics, γ-aminobutyric acid and related amino acid derivatives, bacteriocins, bioactive lipids, and postbiotic components; and (iii) the mechanistic pathways linking these systems to immune, metabolic, endocrine, gastrointestinal, neuroimmune, and aging-related outcomes. Building on these foundations, the review further examines two translational dimensions: precision nutrition, with emphasis on interindividual variability, host–microbiome interactions, responder phenotypes, and product-specific human evidence; and next-generation functional fermented foods, integrating systems-level host–microbiome frameworks, multiomics, emerging predictive technologies, sustainability, safety, and regulatory translation. Microbial–epithelial–immune signaling, short-chain fatty acid receptor activation, regulatory T-cell modulation, intestinal barrier reinforcement, bile acid signaling, and selected fermentation-derived bioactive systems are supported by mechanistic evidence. Strong translational evidence is concentrated in well-characterized product–endpoint combinations, while broad metabolic, endocrine, neurocognitive, neurodegenerative, and healthy-aging claims are heterogeneous, limited, or mostly supported by preclinical and observational evidence. Poor strain-level and process characterization, varied product formulations, limited intervention periods, weak comparators, and extrapolation from isolated microbes or metabolites to whole fermented meals continue to hinder causal interpretation in the literature. Thus, future research should replace generic fermented food categories with reproducible product fingerprints integrating matrix composition, strain-resolved microbial identity, fermentation parameters, viable and non-viable fractions, metabolomic profiles, dose, and host characteristics. To determine which fermented products have clinically meaningful effects, in whom, through which mechanisms, and under what conditions, standardized controlled human interventions, multiomics with causal mediation approaches, precision nutrition frameworks, and integrated safety and regulatory evaluation are needed.