Gut microbe–skin axis on a chip for reproducing the inflammatory crosstalk†

Abstract

The gut–skin axis has emerged as a crucial mediator of skin diseases, with mounting evidence highlighting the influence of gut microbiota on skin health. However, investigating these mechanisms has been hindered by the lack of experimental systems that enable direct study of gut microbiota–skin interactions. Here, we present the gut microbe–skin chip (GMS chip), a novel microfluidic platform designed to model microbiome–gut–skin axis interactions. The GMS chip allows the coculture of intestinal epithelial cells (Caco-2), human epidermal keratinocytes (HEKa), and gut microbes with fluidic connection mimicking the blood flow. We validated that the gut compartment, with a self-sustaining oxygen gradient, enabled coculturing gut bacteria such as Escherichia coli (E. coli) and Lactobacillus rhamnosus GG (LGG), and the skin cells properly differentiated in the chip in the presence of fluid flow. Disruption of intestinal epithelial integrity by dextran sodium sulfate (DSS) combined with lipopolysaccharides (LPS) selectively decreased skin cell viability while sparing gut cells. Notably, pretreatment with LGG showed a protective effect against the skin cell damage by enhancing the intestinal barrier function. The GMS chip effectively recapitulates the influence of gut microbiota on skin health, representing a pivotal step forward in studying gut–skin axis mechanisms and the role of the gut microbiome in skin diseases.