A gut-skin multi-organ-on-a-chip with integrated three-dimensional sebocyte-containing microtissues for studying lipid- and lipopolysaccharide-mediated interorgan crosstalk

초록

Clinical data suggest that gut dysbiosis induced by high-fat diets is associated with skin diseases, but animal and clinical studies have limited mechanistic resolution of these interactions. In vitro multi-organ models offer an experimental platform for dissecting these interactions, yet existing gut-skin models lack sebaceous glands, a key regulator of skin lipid metabolism and lipid-related inflammation. Here, we report a gut-skin multi-organ-on-a-chip model (MOOC) with three-dimensional sebocyte-containing collagen microbeads. The gut-skin MOOC supports co-cultures of a skin compartment (dermal fibroblasts together with sebocyte-loaded collagen beads) and a gut compartment (intestinal epithelium), each differentiated on a cell culture insert. Application of lipopolysaccharide (LPS) lowered the TEER of the intestinal epithelium while preserving tight junction architecture, whereas lipid treatment produced focal disruption of junctional ZO-1, indicating distinct modes of barrier remodeling. Compared to the skin-only model, the gut-skin MOOC exhibited lower TNF-α secretion across all conditions. LPS-induced TNF-α elevation was observed in the skin-only model but not in the gut-skin MOOC. In contrast, lipid treatment increased IL-6 secretion in the gut-skin MOOC but not in the skin-only model. Our study demonstrates that the gut-skin MOOC captures both barrier function and interorgan crosstalk, providing an in vitro platform for testing dermatological interventions that act on the gut-skin axis. © The Author(s), under exclusive licence to The Korean Society for Biotechnology and Bioengineering 2026.

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