Enzymatic Synergy-Driven Biotransformation Generates a Postbiotic-Rich Functional Matrix That Reprograms Gut...

The physiological efficacy of plant-based matrices is often limited because bioactive compounds are sequestered within complex lignocellulosic architectures, restricting their release and downstream activity. Fermentation-driven enzymatic biotransformation can overcome these structural barriers; however, the mechanisms by which fermentation-derived, non-viable functional ingredients (postbiotics) confer benefits remain incompletely defined. Here, we examined whether a postbiotic-rich, co-fermented plant matrix enhances host resilience under metabolic stress and whether such effects are accompanied by a remodeling of gut microbial functional capacity. A functional plant matrix was produced by solid-state co-fermentation using two Lactobacillus plantarum strains selected for complementary lignocellulolytic profiles. Untargeted metabolomics and deep shotgun metagenomic sequencing were integrated with a hydrocortisone-induced murine metabolic stress model to quantify substrate remodeling, host neuroendocrine/behavioral outcomes, and microbiome functional reprogramming. Co-fermentation markedly remodeled the phytochemical landscape, increasing extractable flavonoids and generating distinct metabolite clusters. In vivo, administration of the postbiotic-rich matrix partially normalized stress-responsive neuroendocrine markers (ACTH, TRH, and testosterone) and improved behavioral outcomes in open-field and forced swim assays. These systemic changes were paralleled by a coordinated shift in microbial functional potential, including the enrichment of carbohydrate-active enzyme (CAZyme) families involved in complex polysaccharide utilization (e.g., AA9, GH129, CE14) and attenuation of phosphotransferase system modules and cytochrome P450-related functions. Enzymatic synergy-driven biotransformation yields a postbiotic-rich functional matrix that is associated with a selective remodeling of gut microbiome metabolic potential under stress and concomitant improvement in host physiological resilience. This study underscores microbial functional remodeling as a critical mechanistic interface linking fermentation-modified substrates to host physiological recovery, providing a molecular framework for the development of targeted postbiotic interventions.