Postbiotic mechanisms of long-term fermented soybean foods in host immunometabolic regulation: a critical appraisal of evidence, contradictions, and precision nutrition perspectives

Traditionally made long-term fermented soybean (LTFS) foods, including doenjang, miso, ganjang, and douchi, are produced through months to years of fermentation under high-salinity conditions (12-20% NaCl), generating convergent postbiotic profiles comprising free amino acids, isoflavone aglycones, bioactive peptides, indole derivatives, and gamma-aminobutyric acid. These postbiotics engage host immune, metabolic, and redox signaling through AMPK-SIRT1 activation, NF-kB and RAAS suppression, Nrf2-Keap1 induction, and aryl hydrocarbon receptor signaling. Epidemiological evidence from Korean, Japanese, and Chinese cohorts consistently associates LTFS consumption with improved metabolic outcomes despite high concomitant sodium exposure, suggesting that fermentation-derived bioactive compounds suppress the adverse metabolic consequences of sodium. However, most mechanistic evidence derives from cell and animal models, and human intervention data directly measuring signaling endpoints remain sparse. Gut microbiota biotransformation of LTFS-derived bioactive compounds generates secondary metabolites with distinct biological activities, contributing to substantial inter-individual variability in physiological responses and underscoring the need for precision nutrition approaches that account for individual microbiota composition, metabolic phenotype, and genetic background. This review critically evaluates evidence within a postbiotic-to-signaling framework, distinguishes associative observational findings from preclinical mechanistic evidence, identifies contradictions and null findings, and highlights research priorities including standardized metabolite profiling and human intervention studies with mechanistic biomarker endpoints.