“Good Fences Make Good Neighbors”: How does the Human Gut Microchip Unravel Mechanism of Intestinal Inflammation?

ABSTRACT A microengineered human gut-on-a-chip has demonstrated intestinal physiology, three-dimensional (3D) epithelial morphogenesis, and longitudinal host-microbiome interactions in vitro. The modular accessibility and modularity of the microphysiological gut-on-a-chip can lead to the identification of the seminal trigger in intestinal inflammation. By coupling microbial and immune cells in a spatiotemporal manner, we discovered that the maintenance of healthy epithelial barrier function is necessary and sufficient to demonstrate the homeostatic tolerance of the gut. Here, we highlight the breakthrough of our new disease model and discuss the future impact of investigating the etiology and therapeutic targets in the multifactorial inflammatory bowel disease.

[1]  Donald E Ingber,et al.  Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[2]  C. Romano,et al.  Inflammatory Bowel Disease: Genetics, Epigenetics, and Pathogenesis , 2015, Front. Immunol..

[3]  Donald E Ingber,et al.  Reverse Engineering Human Pathophysiology with Organs-on-Chips , 2016, Cell.

[4]  Dong-Woo Lee,et al.  A Robust Longitudinal Co-culture of Obligate Anaerobic Gut Microbiome With Human Intestinal Epithelium in an Anoxic-Oxic Interface-on-a-Chip , 2019, Front. Bioeng. Biotechnol..

[5]  Woojung Shin,et al.  Human Intestinal Morphogenesis Controlled by Transepithelial Morphogen Gradient and Flow-Dependent Physical Cues in a Microengineered Gut-on-a-Chip , 2019, iScience.

[6]  Abdul W Basit,et al.  Animal Farm: Considerations in Animal Gastrointestinal Physiology and Relevance to Drug Delivery in Humans. , 2015, Journal of pharmaceutical sciences.

[7]  J. Sierra,et al.  Higher Fecal Short-Chain Fatty Acid Levels Are Associated with Gut Microbiome Dysbiosis, Obesity, Hypertension and Cardiometabolic Disease Risk Factors , 2018, Nutrients.

[8]  Jiajie Yu,et al.  Microscale 3-D hydrogel scaffold for biomimetic gastrointestinal (GI) tract model. , 2011, Lab on a chip.

[9]  L. Rigottier-Gois,et al.  Dysbiosis in inflammatory bowel diseases: the oxygen hypothesis , 2013, The ISME Journal.

[10]  Woojung Shin,et al.  Microfluidic Organ-on-a-Chip Models of Human Intestine , 2018, Cellular and molecular gastroenterology and hepatology.

[11]  Nancy L Allbritton,et al.  A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium. , 2017, Biomaterials.

[12]  D. Rubin,et al.  Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. , 2014, Journal of Crohn's & colitis.

[13]  S. D. De Keersmaecker,et al.  Lessons from probiotic-host interaction studies in murine models of experimental colitis. , 2011, Molecular nutrition & food research.

[14]  Maria T. Abreu,et al.  Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function , 2010, Nature Reviews Immunology.

[15]  J. H. I. Huis in't Veld,et al.  Probiotic effects of Lactobacillus casei on DSS-induced ulcerative colitis in mice. , 2005, International journal of food microbiology.

[16]  J. Satsangi,et al.  Pathogenesis of Crohn's disease , 2015, F1000prime reports.

[17]  S. Biswas Does the Interdependence between Oxidative Stress and Inflammation Explain the Antioxidant Paradox? , 2016, Oxidative medicine and cellular longevity.

[18]  D. Ingber,et al.  Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. , 2012, Lab on a chip.

[19]  Michael A McGuckin,et al.  Intestinal barrier dysfunction in inflammatory bowel diseases. , 2009, Inflammatory bowel diseases.

[20]  J. Bakken,et al.  Treating Clostridium difficile infection with fecal microbiota transplantation. , 2011, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[21]  Jeroen Raes,et al.  How informative is the mouse for human gut microbiota research? , 2015, Disease Models & Mechanisms.

[22]  M. Perše,et al.  Dextran Sodium Sulphate Colitis Mouse Model: Traps and Tricks , 2012, Journal of biomedicine & biotechnology.

[23]  L. Peyrin-Biroulet,et al.  Crohn's disease , 2017, The Lancet.

[24]  B. Chassaing,et al.  Dextran Sulfate Sodium (DSS)‐Induced Colitis in Mice , 2014, Current protocols in immunology.

[25]  Woojung Shin,et al.  Intestinal barrier dysfunction orchestrates the onset of inflammatory host–microbiome cross-talk in a human gut inflammation-on-a-chip , 2018, Proceedings of the National Academy of Sciences.

[26]  J. Collins,et al.  Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip , 2015, Proceedings of the National Academy of Sciences.

[27]  F. Collins,et al.  A new initiative on precision medicine. , 2015, The New England journal of medicine.

[28]  Connie Zhao,et al.  Emulating Host-Microbiome Ecosystem of Human Gastrointestinal Tract in Vitro , 2017, Stem Cell Reviews and Reports.

[29]  S. Colgan,et al.  Physiologic hypoxia and oxygen homeostasis in the healthy intestine. A Review in the Theme: Cellular Responses to Hypoxia. , 2015, American journal of physiology. Cell physiology.

[30]  William W. Agace,et al.  Regional specialization within the intestinal immune system , 2014, Nature Reviews Immunology.

[31]  W. Strober,et al.  Experimental Models of Inflammatory Bowel Diseases , 2015, Cellular and molecular gastroenterology and hepatology.

[32]  A. Kunz,et al.  Two cases of Lactobacillus bacteremia during probiotic treatment of short gut syndrome. , 2004, Journal of pediatric gastroenterology and nutrition.

[33]  M. Tang,et al.  Probiotic use in clinical practice: what are the risks? , 2006, The American journal of clinical nutrition.