Peng Chun-Yan, Fang Ting, Lin Hao-Bin, Zhang Ni, Hu Zi-Zi, Wang Hai-Tao, Su Ming-Hui, Sha Xiao-Mei, Tu Zong-Cai
National R&D Center for Freshwater Fish Processing, College of Life Science &School of Health, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.
State Key Laboratory of Marine Food Processing and Safety Control, Dalian Polytechnic University, Qinggongyuan1, Ganjingzi District, Dalian 116034, Liaoning, China.
Food Res Int. 2025 May;209:116295. doi: 10.1016/j.foodres.2025.116295. Epub 2025 Mar 18.
Sustained release technology facilitates precise regulation of active ingredient delivery, attenuating enzymatic degradation while optimizing bioavailability in malabsorptive conditions. Microbial transglutaminase (MTGase) catalyzes isopeptide bond formation via acyl transfer reactions, conferring resistance to gastrointestinal digestion. However, the in vivo sustained release potential of MTGase-modified fish gelatin (MTGase-modified-FG) remains uncertain. In this study, enzymatic modification was performed using MTGase at graded concentrations (0.00 % (Nor), 0.06 % (LD), 0.12 % (MD), and 0.21 % (HD)), with sustained release of collagen evaluated through pharmacokinetic analysis. The results indicated that the MTGase-modified-FG supplementation exhibited a dose-dependent sustained release, extending Tmax from 2.00 ± 0.00 h (Nor) to 5.33 ± 1.15 h (HD). Notably, suboptimal crosslinking (LD/MD) enhanced skin collagen deposition, whereas excessive modification (HD) induced malabsorptive phenomena that may be attributed to the presence of excessive isopeptide bonds. Metabolomic analysis identified MTGase-modified-FG modulated the serum metabolome in collagen-related metabolites (LysoPC, Lysine, succinate), mechanistically linked to choline metabolism in cancer and lysine catabolism. Additionally, the gut microbiota remodeling was modulated by the suppression of Ruminococcus and Blautia, as well as by the expansion of Faecalibaculum and Bifidobacterium at the genus level. RT-qPCR analysis indicated that MTGase-modified-FG enhanced collagen deposition via the TGF-β/Smads and MAPK/AP-1/MMP pathways in human dermal fibroblast cells. These findings suggest that MTGase-modified confers the sustained release properties to fish gelatin, and provides a new collagen supplementation strategy for individuals with malabsorption syndromes.
缓释技术有助于精确调节活性成分的释放，减少酶促降解，同时在吸收不良的情况下优化生物利用度。微生物转谷氨酰胺酶（MTGase）通过酰基转移反应催化异肽键的形成，赋予对胃肠消化的抗性。然而，MTGase修饰的鱼明胶（MTGase修饰-FG）在体内的缓释潜力仍不确定。在本研究中，使用不同浓度（0.00%（Nor）、0.06%（LD）、0.12%（MD）和0.21%（HD））的MTGase进行酶促修饰，并通过药代动力学分析评估胶原蛋白的缓释情况。结果表明，补充MTGase修饰-FG呈现剂量依赖性缓释，将Tmax从2.00±0.00小时（Nor）延长至5.33±1.15小时（HD）。值得注意的是，次优交联（LD/MD）增强了皮肤胶原蛋白沉积，而过度修饰（HD）则引发了吸收不良现象，这可能归因于过多异肽键的存在。代谢组学分析确定MTGase修饰-FG调节了与胶原蛋白相关代谢物（溶血磷脂酰胆碱、赖氨酸、琥珀酸盐）中的血清代谢组，其机制与癌症中的胆碱代谢和赖氨酸分解代谢有关。此外，肠道微生物群重塑通过瘤胃球菌属和布劳特氏菌属的抑制以及粪杆菌属和双歧杆菌属在属水平上的扩张而受到调节。RT-qPCR分析表明，MTGase修饰-FG通过人皮肤成纤维细胞中的TGF-β/Smads和MAPK/AP-1/MMP途径增强胶原蛋白沉积。这些发现表明，MTGase修饰赋予鱼明胶缓释特性，并为吸收不良综合征患者提供了一种新的胶原蛋白补充策略。
