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Updated: Aug 13, 2026
Co-culture of Living Microbiome with Microengineered Human Intestinal Villi in a Gut-on-a-Chip Microfluidic Device
Published on: August 30, 2016
Primary exploration of host-microorganism interaction and enteritis treatment with an embedded membrane microfluidic
Wei Zhao1, Yuhan Yao1, Tong Zhang1
1Shanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, China.
Abstract:
Intestinal flora plays a crucial role in the host's intestinal health. Imbalances in the intestinal flora, when accompanied by inflammation, affect the host's intestinal barrier function. Understanding it requires studying how living cells and tissues work in the context of living organs, but it is difficult to form the three-dimensional microstructure intestinal-vascular system by monolayer cell or co-culture cell models, and animal models are costly and slow. The use of microfluidic-based organ chips is a fast, simple, and high-throughput method that not only solves the affinity problem of animal models but the lack of microstructure problem of monolayer cells. In this study, we designed an embedded membrane chip to generate an in vitro gut-on-a-chip model. Human umbilical vein endothelial cells and Caco-2 were cultured in the upper and lower layers of the culture chambers in the microfluidic chip, respectively. The human peripheral blood mononuclear cells were infused into the capillary side at a constant rate using an external pump to simulate the in vitro immune system and the shear stress of blood in vivo. The model exhibited intestine morphology and function after only 5 days of culture, which is significantly less than the 21 days required for static culture in the Transwell® chamber. Furthermore, it was observed that drug-resistant bacteria triggered barrier function impairment and inflammation, resulting in enteritis, whereas probiotics (Lactobacillus rhamnosus GG) improved only partially. The use of Amikacin for enteritis is effective, whereas other antibiotic therapies do not work, which are consistent with clinical test results. This model may be used to explore intestinal ecology, host and intestinal flora interactions, and medication assessment.
Insights
This study introduces a novel gut-on-a-chip model using microfluidics to rapidly simulate intestinal health and disease. The advanced model effectively replicates intestinal barrier function and inflammation, aiding in drug efficacy testing for enteritis.
Area of Science:
- Biomedical Engineering
- Microfluidics
- Gastroenterology
Background:
- Intestinal flora is vital for gut health, but imbalances and inflammation impair barrier function.
- Traditional models like cell cultures and animal studies have limitations in replicating complex intestinal microenvironments.
- Microfluidic organ-on-a-chip technology offers a faster, more accurate alternative for studying gut physiology and disease.
Purpose of the Study:
- To develop and validate a microfluidic gut-on-a-chip model for simulating intestinal health and disease.
- To assess the model's ability to replicate intestinal morphology, function, and inflammatory responses.
- To evaluate the efficacy of probiotics and antibiotics in treating enteritis using the developed model.
Main Methods:
- An embedded membrane microfluidic chip was designed to create an in vitro gut-on-a-chip model.
- Human umbilical vein endothelial cells and Caco-2 cells were cultured in distinct layers.
- Peripheral blood mononuclear cells were introduced to simulate the immune system and blood shear stress.
Main Results:
- The gut-on-a-chip model achieved intestinal morphology and function within 5 days, significantly faster than static cultures.
- Drug-resistant bacteria induced barrier impairment and inflammation, leading to enteritis.
- Probiotics showed partial improvement, while Amikacin demonstrated effectiveness against enteritis, aligning with clinical findings.
Conclusions:
- The microfluidic gut-on-a-chip model provides a rapid and accurate platform for studying intestinal ecology and host-microbe interactions.
- This model shows potential for evaluating drug efficacy and understanding enteritis mechanisms.
- The technology overcomes limitations of traditional models, offering a more relevant in vitro system for gastrointestinal research.
