Collagen and Hyaluronic Acid Combinations Modulate Intestinal Barrier Function and Skin Extracellular Matrix Responses in a Gut–Skin In Vitro Model

Collagen and hyaluronic acid (HA) are major extracellular matrix (ECM) components involved in skin structure and tissue homeostasis. However, the biological effects of different collagen sources, when combined with HA, following intestinal passage, remain incompletely characterised. This study investigated the effects of bovine and marine collagen hydrolysates and a compositionally distinct biomimetic formulation, each combined with two distinct HA preparations (such as GreenIuronic® and sodium hyaluronate), in an integrated gut–skin in vitro model. Caco-2 intestinal cells were used to assess barrier integrity, fluorescein permeability, basolateral recovery of the measured analytes, oxidative stress and tight junction-related proteins. A skin co-culture model was subsequently exposed to basolateral medium collected from treated Caco-2 cultures and analysed for cell viability and ECM-related endpoints. The tested combinations generally improved transepithelial electrical resistance, passage through the intestinal model, cell viability, and tight junction protein expression compared with untreated controls. Following exposure to basolateral medium collected from treated Caco-2 cultures, the skin co-culture model showed changes in ECM-related measurements, including collagen, elastin and measured HA levels. Combinations containing GreenIuronic® were generally associated with stronger effects under the experimental conditions tested. Western blot analyses further supported modulation of ECM-related proteins, including COL1A1, HAS2, ELN, and MMP1, suggesting a shift towards a matrix-supportive profile. In conclusion, these findings provide preliminary in vitro evidence that collagen-HA combinations may modulate intestinal barrier-related parameters and extracellular matrix-associated measured endpoints within an integrated gut-skin model.