Primary exploration of host–microorganism interaction and enteritis treatment with an embedded membrane microfluidic chip of the human intestinal–vascular microsystem

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...

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Main Authors: Wei Zhao, Yuhan Yao, Tong Zhang, Huijun Lu, Xinlian Zhang, Linlin Zhao, Xi Chen, Jinhui Zhu, Guodong Sui, Wang Zhao
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-12-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2022.1035647/full
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author Wei Zhao
Yuhan Yao
Tong Zhang
Huijun Lu
Xinlian Zhang
Linlin Zhao
Xi Chen
Jinhui Zhu
Guodong Sui
Wang Zhao
author_facet Wei Zhao
Yuhan Yao
Tong Zhang
Huijun Lu
Xinlian Zhang
Linlin Zhao
Xi Chen
Jinhui Zhu
Guodong Sui
Wang Zhao
author_sort Wei Zhao
collection DOAJ
description 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.
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spelling doaj.art-66a6bf525bf9459982ac0536ecef49bb2022-12-22T04:40:01ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-12-011010.3389/fbioe.2022.10356471035647Primary exploration of host–microorganism interaction and enteritis treatment with an embedded membrane microfluidic chip of the human intestinal–vascular microsystemWei Zhao0Yuhan Yao1Tong Zhang2Huijun Lu3Xinlian Zhang4Linlin Zhao5Xi Chen6Jinhui Zhu7Guodong Sui8Wang Zhao9Shanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, ChinaShanghai Changhai Hospital Department of Gastroenterology, Shanghai, ChinaShanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, ChinaIntestinal 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.https://www.frontiersin.org/articles/10.3389/fbioe.2022.1035647/fullgut-on-a-chipembedded membrane chipESBLenteritistreatment
spellingShingle Wei Zhao
Yuhan Yao
Tong Zhang
Huijun Lu
Xinlian Zhang
Linlin Zhao
Xi Chen
Jinhui Zhu
Guodong Sui
Wang Zhao
Primary exploration of host–microorganism interaction and enteritis treatment with an embedded membrane microfluidic chip of the human intestinal–vascular microsystem
Frontiers in Bioengineering and Biotechnology
gut-on-a-chip
embedded membrane chip
ESBL
enteritis
treatment
title Primary exploration of host–microorganism interaction and enteritis treatment with an embedded membrane microfluidic chip of the human intestinal–vascular microsystem
title_full Primary exploration of host–microorganism interaction and enteritis treatment with an embedded membrane microfluidic chip of the human intestinal–vascular microsystem
title_fullStr Primary exploration of host–microorganism interaction and enteritis treatment with an embedded membrane microfluidic chip of the human intestinal–vascular microsystem
title_full_unstemmed Primary exploration of host–microorganism interaction and enteritis treatment with an embedded membrane microfluidic chip of the human intestinal–vascular microsystem
title_short Primary exploration of host–microorganism interaction and enteritis treatment with an embedded membrane microfluidic chip of the human intestinal–vascular microsystem
title_sort primary exploration of host microorganism interaction and enteritis treatment with an embedded membrane microfluidic chip of the human intestinal vascular microsystem
topic gut-on-a-chip
embedded membrane chip
ESBL
enteritis
treatment
url https://www.frontiersin.org/articles/10.3389/fbioe.2022.1035647/full
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