Transglutaminase-Crosslinked Collagen Gel Delays Gastrointestinal Transit and Prolongs Serum Appearance of Antioxidant Collagen Di- and Tripeptides in Mice

Background: Transglutaminase-crosslinked collagen gel (CHG) is a collagen product cross-linked with transglutaminase (TGase) that exhibits good thermal stability and has potential applications in functional food formulations. However, it remains unclear whether the gelation of CHG alters the metabolic fate of collagen-derived bioactive peptides in the gastrointestinal tract and their distribution within the body. Methods: This study investigated the retention of CHG in the gastrointestinal tract of male C57BL/6J mice, as well as its serum peptide levels and antioxidant activity. Results: Compared with unhydrolyzed (CNS) and hydrolyzed collagen (CHS) sols, CHG significantly prolonged gastric retention and slowed intestinal transit, while gastric contents exhibited larger particle sizes and a more sustained release of protein. The CHG also increased the expression of genes associated with Cajal interstitial (ICC) cells in the gastric antrum (HCN1, Trpm7, CX43, and c-kit) and prolonged the secretion of leptin, cholecystokinin, serotonin, and vasoactive intestinal peptide. Serum peptide analysis showed that the concentrations of most collagen dipeptides and tripeptides, peaked between 0.5 and 1.5 h and then gradually declined; notably, the concentration of Pro-Hyp in the CHG group remained higher than that in the control group at 3 h, indicating prolonged serum appearance. Serum peptides from CHG group (particularly Pro-Hyp) exhibited total antioxidant capacity and hydroxyl radical scavenging activity, and the mixed-peptide solution significantly reduced the accumulation of reactive oxygen species in H2O2-induced skin fibroblasts (p < 0.001). Conclusions: These findings suggest that the cross-linked structure of CHG alters gastrointestinal metabolic processes and is associated with the persistent presence of collagen-derived dipeptides and tripeptides in serum.