Divergent metabolic shifts of lactic acid bacteria strains shape the quality and predicted antioxidant mechanisms of a fermented fish-rice matrix (Yucha).

The functional potential of fish-rice co-fermented high-protein matrices remains difficult to harness because of the unpredictability of spontaneous fermentation. This study employed metabolomics and network pharmacology to decode the metabolic reprogramming orchestrated by three lactic acid bacteria strains. Inoculation rapidly stabilized physicochemical properties and mitigated lipid oxidation. Metabolomic profiling revealed distinct strain-specific metabolite profiles: YC202 was associated with differences in carbohydrate-related metabolites and the antioxidant dipeptide carnosine; YDN29 showed higher abundances of umami-associated amino acids; and FY27 showed higher abundances of selected polyunsaturated fatty acids. In vitro antioxidant assays further showed that LAB inoculation increased chemical antioxidant capacity. Bridging these chemical phenotypes to biological functions, network pharmacology integrated 129 bioactive metabolites with 421 oxidative damage-associated targets. The in silico analysis suggested that the identified metabolites may be associated with antioxidant-related PI3K-Akt and MAPK signaling pathways. These findings may support rational LAB selection for standardized fermented aquatic foods.