{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T15:59:33Z","timestamp":1770220773886,"version":"3.49.0"},"reference-count":99,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T00:00:00Z","timestamp":1466985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>The human intestine is a dynamic organ where the complex host-microbe interactions that orchestrate intestinal homeostasis occur. Major contributing factors associated with intestinal health and diseases include metabolically-active gut microbiota, intestinal epithelium, immune components, and rhythmical bowel movement known as peristalsis. Human intestinal disease models have been developed; however, a considerable number of existing models often fail to reproducibly predict human intestinal pathophysiology in response to biological and chemical perturbations or clinical interventions. Intestinal organoid models have provided promising cytodifferentiation and regeneration, but the lack of luminal flow and physical bowel movements seriously hamper mimicking complex host-microbe crosstalk. Here, we discuss recent advances of human intestinal microphysiological systems, such as the biomimetic human \u201cGut-on-a-Chip\u201d that can employ key intestinal components, such as villus epithelium, gut microbiota, and immune components under peristalsis-like motions and flow, to reconstitute the transmural 3D lumen-capillary tissue interface. By encompassing cutting-edge tools in microfluidics, tissue engineering, and clinical microbiology, gut-on-a-chip has been leveraged not only to recapitulate organ-level intestinal functions, but also emulate the pathophysiology of intestinal disorders, such as chronic inflammation. Finally, we provide potential perspectives of the next generation microphysiological systems as a personalized platform to validate the efficacy, safety, metabolism, and therapeutic responses of new drug compounds in the preclinical stage.<\/jats:p>","DOI":"10.3390\/mi7070107","type":"journal-article","created":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T12:56:01Z","timestamp":1467032161000},"page":"107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Farewell to Animal Testing: Innovations on Human Intestinal Microphysiological Systems"],"prefix":"10.3390","volume":"7","author":[{"given":"Tae","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5342-2870","authenticated-orcid":false,"given":"Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrmicro2974","article-title":"The gut microbiota\u2014Masters of host development and physiology","volume":"11","author":"Sommer","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jaci.2009.05.038","article-title":"Intestinal barrier function: Molecular regulation and disease pathogenesis","volume":"124","author":"Groschwitz","year":"2009","journal-title":"J. Allergy Clin. Immun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1097\/BOR.0000000000000190","article-title":"The functional impact of the intestinal microbiome on mucosal immunity and systemic autoimmunity","volume":"27","author":"Longman","year":"2015","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1159\/000076385","article-title":"Paradigms for mechanical signal transduction in the intestinal epithelium. Category: Molecular, cell, and developmental biology","volume":"68","author":"Basson","year":"2003","journal-title":"Digestion"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1172\/JCI108740","article-title":"The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine","volume":"59","author":"Vantrappen","year":"1977","journal-title":"J. Clin. Investig."},{"key":"ref_6","first-page":"E7","article-title":"Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip","volume":"113","author":"Kim","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature11551","article-title":"Reciprocal interactions of the intestinal microbiota and immune system","volume":"489","author":"Maynard","year":"2012","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nri2515","article-title":"The gut microbiota shapes intestinal immune responses during health and disease","volume":"9","author":"Round","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1540\/jsmr.43.43","article-title":"Mechanism of abnormal intestinal motility in inflammatory bowel disease: How smooth muscle contraction is reduced?","volume":"43","author":"Ohama","year":"2007","journal-title":"J. Smooth Muscle Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.cellsig.2009.02.011","article-title":"The effects of mechanical forces on intestinal physiology and pathology","volume":"21","author":"Gayer","year":"2009","journal-title":"Cell. Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S1521-6918(03)00022-2","article-title":"Gastrointestinal disorders of the critically ill. Systemic consequences of ileus","volume":"17","author":"Madl","year":"2003","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrgastro.2012.14","article-title":"IBD-what role do Proteobacteria play?","volume":"9","author":"Mukhopadhya","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1517\/17425240903241788","article-title":"Preclinical models for pulmonary drug delivery","volume":"6","author":"Fernandes","year":"2009","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Patterson, D.M., Shohet, J.M., and Kim, E.S. (2011). Preclinical models of pediatric solid tumors (neuroblastoma) and their use in drug discovery. Curr. Protoc. Pharmacol.","DOI":"10.1002\/0471141755.ph1417s52"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1053\/j.seminoncol.2012.08.006","article-title":"Use of preclinical models to assess the therapeutic potential of new drug candidates for bladder cancer","volume":"39","author":"Amit","year":"2012","journal-title":"Semin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1186\/bcr2441","article-title":"The role of preclinical animal models in breast cancer drug development","volume":"11","author":"Clarke","year":"2009","journal-title":"Breast Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/jps.2600610111","article-title":"Influence of route of administration on drug availability","volume":"61","author":"Rowland","year":"1972","journal-title":"J. Pharm. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2165\/00003088-198409010-00001","article-title":"First-pass elimination. Basic concepts and clinical consequences","volume":"9","author":"Pond","year":"1984","journal-title":"Clin. Pharmacokinet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.2165\/11317030-000000000-00000","article-title":"Efflux-mediated drug resistance in bacteria: An update","volume":"69","author":"Li","year":"2009","journal-title":"Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1517\/17425255.2013.807798","article-title":"The effect of gut microbiota on drug metabolism","volume":"9","author":"Kang","year":"2013","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"183","DOI":"10.4161\/gmic.28403","article-title":"Broad scope method for creating humanized animal models for animal health and disease research through antibiotic treatment and human fecal transfer","volume":"5","author":"Hintze","year":"2014","journal-title":"Gut Microbes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1073\/pnas.1222878110","article-title":"Genomic responses in mouse models poorly mimic human inflammatory diseases","volume":"110","author":"Seok","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/978-1-60761-720-4_21","article-title":"Assessing inflammatory disease at mucosal surfaces in murine genetic models","volume":"900","author":"Engelman","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/nbt.2858","article-title":"Development and function of human innate immune cells in a humanized mouse model","volume":"32","author":"Rongvaux","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nature06005","article-title":"Unravelling the pathogenesis of inflammatory bowel disease","volume":"448","author":"Xavier","year":"2007","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/S0140-6736(07)60750-8","article-title":"Inflammatory bowel disease: Cause and immunobiology","volume":"369","author":"Baumgart","year":"2007","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S1359-6446(04)03354-9","article-title":"Cell culture-based models for intestinal permeability: A critique","volume":"10","author":"Balimane","year":"2005","journal-title":"Drug Discov. Today"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1038\/nprot.2007.303","article-title":"Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers","volume":"2","author":"Hubatsch","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1136\/gut.47.1.79","article-title":"Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell\/leucocyte co-cultures","volume":"47","author":"Haller","year":"2000","journal-title":"Gut"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nnano.2012.3","article-title":"Oral exposure to polystyrene nanoparticles affects iron absorption","volume":"7","author":"Mahler","year":"2012","journal-title":"Nat. Nanotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1039\/c2lc40074j","article-title":"Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow","volume":"12","author":"Kim","year":"2012","journal-title":"Lab Chip"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1039\/c3ib40126j","article-title":"Gut-on-a-chip microenvironment induces human intestinal cells to undergo villus differentiation","volume":"5","author":"Kim","year":"2013","journal-title":"Integr. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nrm2236","article-title":"The third dimension bridges the gap between cell culture and live tissue","volume":"8","author":"Pampaloni","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7586","DOI":"10.1016\/j.biomaterials.2010.06.036","article-title":"Synergic effects of crypt-like topography and ECM proteins on intestinal cell behavior in collagen based membranes","volume":"31","author":"Wang","year":"2010","journal-title":"Biomaterials"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1002\/bit.24518","article-title":"In vitro 3D human small intestinal villous model for drug permeability determination","volume":"109","author":"Yu","year":"2012","journal-title":"Biotechnol. Bioeng."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6825","DOI":"10.1016\/j.biomaterials.2009.08.046","article-title":"Influence of micro-well biomimetic topography on intestinal epithelial Caco-2 cell phenotype","volume":"30","author":"Wang","year":"2009","journal-title":"Biomaterials"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1039\/C0LC00273A","article-title":"Microscale 3-D hydrogel scaffold for biomimetic gastrointestinal (GI) tract model","volume":"11","author":"Sung","year":"2011","journal-title":"Lab Chip"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1002\/bit.25180","article-title":"Synthetic small intestinal scaffolds for improved studies of intestinal differentiation","volume":"111","author":"Costello","year":"2014","journal-title":"Biotechnol. Bioeng."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1053\/j.gastro.2010.03.002","article-title":"Leucine-rich repeat-containing g-protein-coupled receptors as markers of adult stem cells","volume":"138","author":"Barker","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1234852","article-title":"Growing self-organizing mini-guts from a single intestinal stem cell: Mechanism and applications","volume":"340","author":"Sato","year":"2013","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1053\/j.gastro.2011.07.050","article-title":"Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and barrett\u2019s epithelium","volume":"141","author":"Sato","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche","volume":"459","author":"Sato","year":"2009","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature09691","article-title":"Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro","volume":"470","author":"Spence","year":"2011","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.cell.2015.03.053","article-title":"Prospective derivation of a living organoid biobank of colorectal cancer patients","volume":"161","author":"Francies","year":"2015","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/scrt362","article-title":"Building additional complexity to in vitro-derived intestinal tissues","volume":"4","author":"Brugmann","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1128\/IAI.02561-14","article-title":"Persistence and toxin production by clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function","volume":"83","author":"Leslie","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"G497","DOI":"10.1152\/ajpgi.00090.2014","article-title":"Human clostridium difficile infection: Inhibition of NHE3 and microbiota profile","volume":"308","author":"Engevik","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"G510","DOI":"10.1152\/ajpgi.00091.2014","article-title":"Human clostridium difficile infection: Altered mucus production and composition","volume":"308","author":"Engevik","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"G1359","DOI":"10.1152\/ajpgi.00493.2011","article-title":"A nomenclature for intestinal in vitro cultures","volume":"302","author":"Stelzner","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e00159","DOI":"10.1128\/mBio.00159-12","article-title":"Stem cell-derived human intestinal organoids as an infection model for rotaviruses","volume":"3","author":"Finkbeiner","year":"2012","journal-title":"MBio"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"396","DOI":"10.3201\/eid1303.060549","article-title":"In vitro cell culture infectivity assay for human noroviruses","volume":"13","author":"Straub","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/nm.3201","article-title":"A functional cftr assay using primary cystic fibrosis intestinal organoids","volume":"19","author":"Dekkers","year":"2013","journal-title":"Nat. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1177\/1535370214529398","article-title":"Human enteroids as an ex vivo model of host-pathogen interactions in the gastrointestinal tract","volume":"239","author":"In","year":"2014","journal-title":"Exp. Biol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"S286","DOI":"10.1016\/S0016-5085(14)61014-3","article-title":"Sa1743 EHEC virulence factor espp cleaves actin binding protein fodrin to induce macropinocytosis of shiga toxins","volume":"146","author":"In","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.copbio.2013.10.005","article-title":"Microfluidic cell culture","volume":"25","author":"Mehling","year":"2014","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nprot.2009.234","article-title":"Soft lithography for micro- and nanoscale patterning","volume":"5","author":"Qin","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1039\/b717091b","article-title":"An integrated microfluidic system for long-term perfusion culture and on-line monitoring of intestinal tissue models","volume":"8","author":"Kimura","year":"2008","journal-title":"Lab Chip"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.2116\/analsci.25.1403","article-title":"A microfluidic system to evaluate intestinal absorption","volume":"25","author":"Imura","year":"2009","journal-title":"Anal. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.jnutbio.2008.05.006","article-title":"Characterization of Caco-2 and HT29-MTX cocultures in an in vitro digestion\/cell culture model used to predict iron bioavailability","volume":"20","author":"Mahler","year":"2009","journal-title":"J. Nutr. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1007\/s10544-012-9669-0","article-title":"On chip porous polymer membranes for integration of gastrointestinal tract epithelium with microfluidic \u2018body-on-a-chip\u2019 devices","volume":"14","author":"Esch","year":"2012","journal-title":"Biomed. Microdevices"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0889-8553(21)00683-X","article-title":"Small intestinal physiology and pathophysiology","volume":"18","author":"Sarna","year":"1989","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1039\/B911367C","article-title":"Co-culture of epithelial cells and bacteria for investigating host-pathogen interactions","volume":"10","author":"Kim","year":"2010","journal-title":"Lab Chip"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1007\/s10544-013-9796-2","article-title":"A polymeric cell stretching device for real-time imaging with optical microscopy","volume":"15","author":"Huang","year":"2013","journal-title":"Biomed. Microdevices"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"543","DOI":"10.2217\/nnm.13.45","article-title":"Multiarray cell stretching platform for high-magnification real-time imaging","volume":"8","author":"Huang","year":"2013","journal-title":"Nanomedicine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1038\/nprot.2013.137","article-title":"Microfabrication of human organs-on-chips","volume":"8","author":"Huh","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1146\/annurev-pathol-012414-040418","article-title":"Engineered in vitro disease models","volume":"10","author":"Benam","year":"2015","journal-title":"Annu. Rev. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1021\/jm901846t","article-title":"How well can the Caco-2\/madin-darby canine kidney models predict effective human jejunal permeability?","volume":"53","author":"Avdeef","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.3748\/wjg.v16.i24.2978","article-title":"Small intestinal bacterial overgrowth syndrome","volume":"16","author":"Bures","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1136\/gut.2004.044834","article-title":"Synbiotic therapy (Bifidobacterium longum\/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: A randomised controlled pilot trial","volume":"54","author":"Furrie","year":"2005","journal-title":"Gut"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1136\/gut.2003.037747","article-title":"Maintaining remission of ulcerative colitis with the probiotic Escherichia coli nissle 1917 is as effective as with standard mesalazine","volume":"53","author":"Kruis","year":"2004","journal-title":"Gut"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"435268","DOI":"10.1155\/2013\/435268","article-title":"Gut microbial flora, prebiotics, and probiotics in IBD: Their current usage and utility","volume":"2013","author":"Scaldaferri","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/ibd.22964","article-title":"Clostridium difficile infection in the inflammatory bowel disease patient","volume":"19","author":"Berg","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1159\/000051918","article-title":"Helicobacter pylori infection increases mucosal permeability of the stomach and intestine","volume":"63","author":"Fukuda","year":"2001","journal-title":"Digestion"},{"key":"ref_74","first-page":"126","article-title":"Stimulant-dependent modulation of cytokines and chemokines by airway epithelial cells: Cross talk between pulmonary epithelial and peripheral blood mononuclear cells","volume":"9","author":"Krakauer","year":"2002","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1365-2567.2004.01874.x","article-title":"Differential effect of immune cells on non-pathogenic gram-negative bacteria-induced nuclear factor-\u03bab activation and pro-inflammatory gene expression in intestinal epithelial cells","volume":"112","author":"Haller","year":"2004","journal-title":"Immunology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/467410a","article-title":"Host-microbe interaction: Inflammation for growth","volume":"467","author":"Miller","year":"2010","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1053\/j.gastro.2014.10.023","article-title":"Microbial therapy in liver disease: Probiotics probe the microbiome-gut-liver-brain axis","volume":"147","author":"Victor","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.tins.2013.01.005","article-title":"Gut-brain axis: How the microbiome influences anxiety and depression","volume":"36","author":"Foster","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9983","DOI":"10.1021\/ac100806x","article-title":"Micro total bioassay system for ingested substances: Assessment of intestinal absorption, hepatic metabolism, and bioactivity","volume":"82","author":"Imura","year":"2010","journal-title":"Anal. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"197","DOI":"10.2116\/analsci.28.197","article-title":"Micro total bioassay system for oral drugs: Evaluation of gastrointestinal degradation, intestinal absorption, hepatic metabolism, and bioactivity","volume":"28","author":"Imura","year":"2012","journal-title":"Anal. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1002\/bit.25232","article-title":"First pass intestinal and liver metabolism of paracetamol in a microfluidic platform coupled with a mathematical modeling as a means of evaluating adme processes in humans","volume":"111","author":"Prot","year":"2014","journal-title":"Biotechnol. Bioeng."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"15015","DOI":"10.1038\/micronano.2015.15","article-title":"An openable artificial intestinal tract system for the in vitro evaluation of medicines","volume":"1","author":"Konishi","year":"2015","journal-title":"Microsyst. Nanoeng."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/aps.2010.120","article-title":"Research and development of next generation of antibody-based therapeutics","volume":"31","author":"Li","year":"2010","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1586\/eci.12.91","article-title":"Current status of monoclonal antibody therapy for the treatment of inflammatory bowel disease: An update","volume":"9","author":"Denmark","year":"2013","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/mi.2012.24","article-title":"The role of neutrophils during intestinal inflammation","volume":"5","author":"Fournier","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nri2155","article-title":"FcRn: The neonatal Fc receptor comes of age","volume":"7","author":"Roopenian","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1203\/00006450-200302000-00015","article-title":"Distribution of the IgG Fc receptor, FcRn, in the human fetal intestine","volume":"53","author":"Shah","year":"2003","journal-title":"Pediatr. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1046\/j.1365-2567.1997.00326.x","article-title":"Expression of the neonatal Fc receptor, FcRn, on human intestinal epithelial cells","volume":"92","author":"Israel","year":"1997","journal-title":"Immunology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1172\/JCI6968","article-title":"Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line","volume":"104","author":"Dickinson","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1007\/s11095-013-1212-3","article-title":"Human and non-human primate intestinal FcRn expression and immunoglobulin G transcytosis","volume":"31","author":"Hornby","year":"2014","journal-title":"Pharm. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.immuni.2004.05.007","article-title":"Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells","volume":"20","author":"Yoshida","year":"2004","journal-title":"Immunity"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00281-006-0054-z","article-title":"IgG transport across mucosal barriers by neonatal Fc receptor for IgG and mucosal immunity","volume":"28","author":"Yoshida","year":"2006","journal-title":"Springer Semin. Immunopathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.it.2006.05.004","article-title":"Perspective\u2014FcRn transports albumin: Relevance to immunology and medicine","volume":"27","author":"Anderson","year":"2006","journal-title":"Trends Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nature13793","article-title":"Artificial sweeteners induce glucose intolerance by altering the gut microbiota","volume":"514","author":"Suez","year":"2014","journal-title":"Nature"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/nature06245","article-title":"An ecological and evolutionary perspective on human-microbe mutualism and disease","volume":"449","author":"Dethlefsen","year":"2007","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Mugambi, M.N., Young, T., and Blaauw, R. (2014). Application of evidence on probiotics, prebiotics and synbiotics by food industry: A descriptive study. BMC Res. Notes, 7.","DOI":"10.1186\/1756-0500-7-754"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/MOG.0000000000000151","article-title":"Prebiotics, probiotics, synbiotics, and the immune system: Experimental data and clinical evidence","volume":"31","author":"Frei","year":"2015","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fmicb.2016.00010","article-title":"Therapeutic application of synbiotics, a fusion of probiotics and prebiotics, and biogenics as a new concept for oral candida infections: A mini review","volume":"7","author":"Ohshima","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1056\/NEJMp1500523","article-title":"A new initiative on precision medicine","volume":"372","author":"Collins","year":"2015","journal-title":"N. Engl. J. Med."}],"container-title":["Micromachines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-666X\/7\/7\/107\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:24:50Z","timestamp":1760210690000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-666X\/7\/7\/107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,27]]},"references-count":99,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2016,7]]}},"alternative-id":["mi7070107"],"URL":"https:\/\/doi.org\/10.3390\/mi7070107","relation":{},"ISSN":["2072-666X"],"issn-type":[{"value":"2072-666X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,27]]}}}