Collagen peptides (CP) have been reported to stimulate dermal collagen synthesis through modulation of the gut microbiota in animal studies, but human evidence remains limited. This study aimed to comprehensively evaluate the clinical efficacy and multi-omics effects of oral CP in humans, integrating skin, gut, and metabolomic analyses. In this 8-week randomized, double-blind, placebo-controlled trial, 70 healthy women (39.2 ± 8.8 years) received CP, a collagen–elastin peptide mixture (MP), or placebo. Significant improvements from baseline were observed in facial wrinkle, texture, hydration, and elasticity in the CP and MP groups (wrinkle: 12.00% and 14.83%; texture: 15.21% and 16.87%; hydration: 4.36 and 4.48 units; elasticity: both 0.10 units), whereas no significant improvements were detected in the PL group (P < 0.05). No significant differences were observed between the CP and MP groups, while more pronounced improvements were detected in women older than 40 years. CP supplementation increased the abundance of Cutibacterium and Lactobacillus in the skin microbiota, and altered skin metabolite profiles, characterized by elevated N-undecanoylglycine and Pro-Pro. CP also increased the abundance of gut Roseburia and Faecalibacterium, enhanced the Gut Microbiome Wellness Index, and enriched amino acid metabolism. Skin improvements correlated with the abundance of Roseburia intestinalis, indicating a gut–skin link. These findings indicate that oral collagen peptides represent a promising strategy for improving skin aging by modulating gut–skin microbiota and metabolomic profiles.

Diabetic cardiomyopathy (DCM) refers diabetic patients develop cardiomyopathy characterized by cardiac systolic and diastolic dysfunction. Currently, no research has explored the role of ten-eleven translocation (TET)-mediated active DNA demethylation in the development of DCM. Through case-control study, we found that the level of 5-hydroxymethylcystein in peripheral blood DNA of DCM patients was significantly lower than it in the healthy subjects and diabetic patients. Secondly, we had conducted an animal study to explore the effect of thinned young apple polyphenol (TYAP) on DNA demethylation in streptococci-induced diabetic mice. TYAP effectively prevented the ventricular dysfunction and cardiomycyte disarray via alleviating DNA epigenetic modifications metabolic disorders in diabetic mice heart. TYAP increased the stability of TET2 protein via activating phosphorylate AMPK and enhanced the activity of TETs enzymes via improving tricarboxylic acid cycle, then promoted TET-mediated active DNA demethylation. TYAP prevented the occurrence of DCM by promoting TET2-mediated active DNA demethylation in the heart of diabetic mice.

The aim of this study was to investigate whether punicalagin (PU) could prevent obesity-related cardiac dysfunction by promoting DNA demethylation, and to explore its possible mechanism. C57BL/6J mice were fed with standard diet, high-fat diet (HFD), HFD supplemented with resveratrol, low-dose PU (LPU) and high-dose PU (HPU) for 8 weeks. Compared with HFD group, body weight was signif icantly lower in PU treatment groups, number of cardiomyocytes and the protein level of myosin heavy chain 7B were signif icantly higher in PU treatment groups. Levels of 5-hydroxymethylcytosine and 5-formylcytosine were signif icantly lower in HFD group than in other groups. Compared with the HFD group, the protein level of ten-eleven translocation enzyme (TET) 2 was significantly higher in PU treatment groups, p-AMP-activated protein kinase (AMPK) was signif icantly higher in LPU group. Levels of total antioxidant capacity and the protein levels of complexes Ⅱ/Ⅲ/Ⅴ, oxoglutarate dehydrogenase, succinate dehydrogenase B and fumarate hydrolase were signif icantly lower in HFD group than PU treatment group. The ratio of (succinic acid + fumaric acid)/α-ketoglutarate was signif icantly higher in HFD group than other groups. In conclusion, PU up-regulated TETs enzyme activities and TET2 protein stability through alleviating mitochondrial dysfunction and activating AMPK, so as to promote DNA demethylation, thus preventing obesity-related cardiac dysfunction.