Collagen peptides promote skin collagen synthesis by modulating the gut microbiota and activating the TGF-β pathway

Collagen peptides have shown potential in improving skin conditions. Based on this, we hypothesized that the protease-resistant portion of these peptides might act as a prebiotic to enhance collagen synthesis by modulating the gut microbiota and activating the TGF-β pathway. <i>In vivo</i> rat models and everted gut sac experiments demonstrated that hydroxyproline-containing tripeptide-rich collagen peptides (CTP) exhibited superior absorption compared to high molecular weight collagen peptides. In a skin collagen-deficient mouse model, CTP supplementation significantly increased skin collagen content by 119.95% compared to the control group. Transcriptomic analysis showed that CTP enhanced skin collagen synthesis and inhibited inflammation-related collagen degradation through the TGF-β pathway, involving anti-inflammatory cells such as plasma cells. Gut microbiota analysis showed that CTP increased the gut microbiota α diversity (Shannon index) and altered the microbial community structure (UniFrac distances), characterized by increased abundance of short-chain fatty acid (SCFA)-producing bacteria, <i>Lachnoclostridium</i> and <i>Roseburia</i>, and enhanced SCFA production. These effects were linked to the delivery of Pro-Hyp to the hindgut according to metabolome analysis, promoting TGF-β-producing cells in the gut and contributing to activation of the TGF-β pathway in the skin. Overall, our study provides novel insights into the mechanism by which CTP promotes skin collagen synthesis through gut microbiota remodeling and TGF-β pathway activation, highlighting the potential of CTP to exhibit prebiotic-like properties for skin health improvement.