Microbial fermentation is an effective strategy to enhance the functional value of plant-derived ingredients. In this study, Stevia rebaudiana leaves were subjected to microbial fermentation to improve their antioxidant potential and functional properties. A composite fermentation system composed of Bacillus subtilis and Candida utilis was established through strain screening, and fermentation conditions were optimized using single-factor and orthogonal experiments, with chlorogenic acid (CA) content and antioxidant activity as evaluation indices. The optimal conditions were determined to be a fermentation temperature of 34 °C, a duration of 36 h, a microbial ratio (Bs:Cu) of 2:1, a moisture content of 55%, and an inoculum level of 3%. Under these optimal conditions, fermentation significantly increased CA content, total phenolic and flavonoid levels, and antioxidant capacity compared with unfermented material. Untargeted metabolomic analysis revealed extensive fermentation-induced remodeling of secondary metabolites, particularly phenolic acids, flavonoids, and terpenoids, including the generation of multiple newly formed bioactive compounds. Functional validation using a laying hen model demonstrated that fermented S. rebaudiana exhibited enhanced antioxidant and anti-inflammatory status and favorable modulation of physiological indicators compared with unfermented samples. Overall, this study demonstrates that microbial consortium fermentation effectively transforms S. rebaudiana from a sweetener-oriented plant into a multifunctional, fermentation-derived functional ingredient. This research is significant as it provides a dual-purpose strategy for developing antioxidant-enriched functional foods for humans and health-promoting natural feed additives for the livestock industry.

Marine-derived collagen peptides exhibit potent intestinal barrier protection; however, their gastrointestinal fate and molecular targets remain unclear, limiting their practical applications. This study investigated the digestive stability and transepithelial transport of GPSGPQGSR, a mucoprotective peptide from Alaska pollock (Gadus chalcogrammus) skin, using simulated gastrointestinal digestion, a Caco-2 cell transport model, and an UPLC-QTOF-MS/MS. The results showed that GPSGPQGSR was a digestion-resistant peptide that reached the intestinal epithelium intact. Although brush border membrane enzymes partially hydrolysed the peptide, 42.16% of intact GPSGPQGSR remained in the luminal compartment after 2 h of incubation. No intact peptide was detected in the basolateral compartment. Molecular docking and 100 ns molecular dynamics simulations identified TLR2 (−14.936 kcal/mol) and PAR2 (−10.154 kcal/mol) as high-affinity extracellular targets of GPSGPQGSR, with stable peptide–receptor interactions and extensive hydrogen bonding networks between the peptide and each receptor (RMSD of 1.8 Å and 2.2 Å, respectively). Pharmacological blockade of TLR2 or PAR2 abolished the protective effects of GPSGPQGSR. These findings demonstrate that GPSGPQGSR acts as a digestion-resistant extracellular signalling peptide that reaches the intestinal epithelium intact and protects barrier function through apical TLR2 and PAR2, providing a mechanistic basis for the rational development of marine collagen peptides for improving intestinal health.