Skin diseases like atopic dermatitis and psoriasis have been linked to gut health, yet the mechanisms behind this gut–skin connection remain poorly understood. Clinical evidence suggests that an imbalance in gut microbes (dysbiosis) can disrupt the intestinal barrier, leading to skin inflammation. However, it has been difficult to directly study how live gut bacteria influence the skin, as existing models often lack the complexity to mimic this interaction.
To address this gap, researchers developed the Gut Microbe–Skin (GMS) chip, a microfluidic chip that integrates gut epithelial cells, human skin cells, and gut microbes. This chip allows scientists to investigate how microbial communities in the gut affect skin cells through a shared fluidic connection, simulating the circulation of bacterial by-products and inflammatory molecules.
“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. “, the authors explained.
The microfluidic device is composed of two compartments: one housing intestinal epithelial cells (Caco-2) and the other containing reconstructed human epidermal keratinocytes (HEKa). The gut compartment features a self-sustaining oxygen gradient, enabling the coculture of both anaerobic and aerobic gut bacteria like Escherichia coli and Lactobacillus rhamnosus GG (LGG).
“Configuration of the gut microbes–skin axis chip (GMS chip). (A) The schematic diagram of the entire chip. (B) The schematic diagram of the intestinal oxygen gradient in vivo. (C) The assembly (left) and the cross-sectional (right) diagram of the gut compartment. (D) Annotated exploded view of the GMS chip. (E) The photographic image of the gravity-driven flow machine. (F) The photographic image of the GMS chip.” Reproduced from B. Ko, J. Son, J. In Won, B. M. Kang, C. W. Choi, R. Kim and J. H. Sung, Lab Chip, 2025, 25, 2609 DOI: 10.1039/D4LC01010H with permission from Royal Society of Chemistry.
Fluid flow between the gut and skin compartments in the microfluidic chip mimics blood circulation, allowing molecules like lipopolysaccharide (LPS) to transfer from the gut to the skin. The gut and skin tissues were first cultured separately to allow proper differentiation and then integrated into the microfluidic chip for coculture studies. The system operated without pumps, using gravity-driven flow to maintain circulation.
The researchers simulated intestinal inflammation by disrupting the gut barrier using dextran sodium sulfate (DSS) and LPS. This treatment reduced skin cell viability, demonstrating that gut barrier dysfunction negatively affects the skin. However, when the gut compartment was pretreated with the probiotic LGG, the gut barrier was reinforced, and skin cell damage was significantly reduced. This protective effect was linked to LGG’s ability to strengthen intestinal tight junctions and decrease the leakage of harmful molecules.
“Viability of Caco-2 cells under the oxygen gradient. (A) The simulated and (B) the measured oxygen concentrations of the culture medium in the cell culture inserts with plugs installed. The symbols and lines indicate the measured and simulated oxygen concentrations, respectively. (C) The representative images of viability assay on Caco-2 cells and (D) cell viability quantified from the cell viability assay. Calcein AM and EthD-1 were used for staining live and dead cells, respectively. n = 3, an unpaired t-test was used for statistical analysis.” Reproduced from B. Ko, J. Son, J. In Won, B. M. Kang, C. W. Choi, R. Kim and J. H. Sung, Lab Chip, 2025, 25, 2609 DOI: 10.1039/D4LC01010H with permission from Royal Society of Chemistry.
The GMS microfluidic chip successfully recreated key features of the gut–skin axis, demonstrating that gut microbes can influence skin health by modulating intestinal barrier integrity. This platform provides a powerful new tool for studying gut–skin interactions and evaluating potential probiotic therapies for skin diseases. By capturing the complex crosstalk between these two organs, the GMS chip opens the door to better understanding and treatment of microbiome-related skin disorders.
“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. “, the authors concluded
Figures are reproduced from B. Ko, J. Son, J. In Won, B. M. Kang, C. W. Choi, R. Kim and J. H. Sung, Lab Chip, 2025, 25, 2609 DOI: 10.1039/D4LC01010H with permission from Royal Society of Chemistry.
Read the original article: Gut microbe–skin axis on a chip for reproducing the inflammatory crosstalk
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