[1] FITZGERALD K A, MALHOTRA M, CURTIN C M, et al. Life in 3D is never flat: 3D models to optimise drug delivery[J]. J Control Release, 2015, 215:39-54. doi:  10.1016/j.jconrel.2015.07.020
[2] PREKSHA G, YESHESWINI R, SRIKANTH C V. Cell culture techniques in gastrointestinal research: Methods, possibilities and challenges[J]. Indian J Pathol Microbiol, 2021, 64(Supplement):S52-S57.
[3] LI X G, CHEN M X, ZHAO S Q, et al. Intestinal Models for Personalized Medicine: from Conventional Models to Microfluidic Primary Intestine-on-a-chip[J]. Stem Cell Rev Rep, 2022, 18(6):2137-2151. doi:  10.1007/s12015-021-10205-y
[4] MOYSIDOU C M, OWENS R M. Advances in modelling the human microbiome-gut-brain axis in vitro[J]. Biochem Soc Trans, 2021, 49(1):187-201. doi:  10.1042/BST20200338
[5] HEWES S A, WILSON R L, ESTES M K, et al. In Vitro Models of the Small Intestine: Engineering Challenges and Engineering Solutions[J]. Tissue Eng Part B Rev, 2020, 26(4):313-326. doi:  10.1089/ten.teb.2019.0334
[6] WALTHER A, COOTS A, NATHAN J, et al. Physiology of the small intestine after resection and transplant[J]. Curr Opin Grastroenterol, 2013, 29(2):153-158.
[7] PETERSON L W, ARTIS D. Intestinal epithelial cells: regulators of barrier function and immunehomeostasis[J]. Nat Rev Immunol, 2014, 14(3):141-153. doi:  10.1038/nri3608
[8] DUTTON J S, HINMAN S S, KIM R, et al. Primary Cell-Derived Intestinal Models: Recapitulating Physiology[J]. Trends Biotechnol, 2019, 37(7):744-760. doi:  10.1016/j.tibtech.2018.12.001
[9] VOLK N, LACY B. Anatomy and Physiology of the Small Bowel[J]. Gastrointest Endosc Clin N Am, 2017, 27(1):1-13.
[10] WORTHINGTON J J, REIMANN F, GRIBBLE F M. Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity[J]. Mucosal Immunol, 2018, 11(1):3-20. doi:  10.1038/mi.2017.73
[11] TAYLOR N C, DRAGET K I. Dynamic responses in small intestinal mucus: Relevance for the maintenance of anintact barrier[J]. Eur J Pharm Biopharm, 2015, 95(Pt A): 144-150.
[12] FURNESS J B, RIVERA L R, CHO H J, et al. The gut as a sensory organ[J]. Nat Rev Gastroenterol Hepatol, 2013, 10(12):729-740. doi:  10.1038/nrgastro.2013.180
[13] 王希, 廖吕钊, 江荣林. 肠上皮细胞紧密连接蛋白的结构功能及其调节[J]. 浙江医学, 2018, 40(8):895-898. doi:  10.12056/j.issn.1006-2785.2017.40.8.2017-1901
[14]

CANALI M M, PEDROTTI L P, BALSINDE J, et al. Chitosan enhances transcellular permeability in human and rat intestine epithelium[J]. Eur J Pharm Biopharm, 2012, 80(2):418-425. doi:  10.1016/j.ejpb.2011.11.007
[15] 杨巨如. 白术多糖对吊尾大鼠肠道黏膜屏障的防护及机制研究[D]. 哈尔滨:哈尔滨工业大学, 2021.
[16]

DONALDSON G P, LEE S M, MAZMANIAN S K. Gut biogeography of the bacterial microbiota[J]. Nat Rev Microbiol, 2016, 14(1):20-32. doi:  10.1038/nrmicro3552
[17] FANG G C, LU H X, AL-NAKASHLI R, et al. Enabling peristalsisof human colon tumor organoids on microfluidic chips[J]. Biofabrication, 2021, 14(1): 015006

FANG G C, LU H X, AL-NAKASHLI R, et al. Enabling peristalsisof human colon tumor organoids on microfluidic chips[J]. Biofabrication, 2021, 14(1):015006
[18]

LIU X. Transporter-mediated drug-drug interactions and their significance[J]. Adv Exp Med Biol, 2019, 1141:241-291.
[19]

ESTUDANTE M, MORAIS J G, SOVERAL G, et al. Intestinal drug transporters: an overview[J]. Adv Drug Deliv Rev, 2013, 65(10):1340-1356. doi:  10.1016/j.addr.2012.09.042
[20]

BEIN A, SHIN W, JALILI-FIROOZINEZHAD S, et al. Microfluidic Organ-on-a-Chip Models of Human Intestine[J]. Cell Mol Gastroenterol Hepatol, 2018, 5(4):659-668.
[21]

LI N, WANG D, SUI Z, et al. Development of an improved three-dimensional in vitro intestinal mucosa model fordrug absorption evaluation[J]. Tissue Eng Part C Methods, 2013, 19(9):708-719. doi:  10.1089/ten.tec.2012.0463
[22]

YU J, PENG S, LUO D, et al. In vitro 3D human small intestinal villous model for drug permeabilitydetermination[J]. Biotechnol Bioeng, 2012, 109(9):2173-2178.
[23]

ALAM M A, AL-JENOOBI F I, AL-MOHIZEA A M. Everted gut sac model as a tool in pharmaceutical research: limitations and applications[J]. J Pharm Pharmacol, 2012, 64(3):326-336. doi:  10.1111/j.2042-7158.2011.01391.x
[24]

HERRMANN J R, TURNER J R. Beyond Ussing's chambers: contemporary thoughts on integration of transepithelial transport[J]. Am J Physiol Cell Physiol, 2016, 310(6):C423-C431. doi:  10.1152/ajpcell.00348.2015
[25]

STEVENS L J, van LIPZIG M, ERPELINCK S, et al. A higher throughput and physiologically relevant two-compartmental human ex vivo intestinal tissue system for studying gastrointestinal processes[J]. Eur J Pharm Sci, 2019, 137:104989. doi:  10.1016/j.ejps.2019.104989
[26]

DONKERS J M, ESLAMI AMIRABADI H, van de STEEG E. Intestine-on-a-chip: Next level in vitro research model of the human intestine[J]. Current Opinion in Toxicology, 2021, 25:6-14. doi:  10.1016/j.cotox.2020.11.002
[27]

KIMURA H, YAMAMOTO T, SAKAI H, et al. An integrated microfluidic system for long-term perfusion culture and on-linemonitoring of intestinal tissue models[J]. Lab Chip, 2008, 8(5):741-746. doi:  10.1039/b717091b
[28]

SHAH P, FRITZ J V, GLAAB E, et al. A microfluidics-based in vitro model of the gastrointestinal human-microbeinterface[J]. Nat Commun, 2016, 7:11535. doi:  10.1038/ncomms11535
[29]

SHIM K Y, LEE D, HAN J, et al. Microfluidic gut-on-a-chip with three-dimensional villi structure[J]. Biomed Microdevices, 2017, 19(2):37. doi:  10.1007/s10544-017-0179-y
[30]

COSTELLO C M, PHILLIPSEN M B, HARTMANIS L M, et al. Microscale Bioreactors for in situ characterization of GI epithelial cellphysiology[J]. Sci Rep, 2017, 7(1):12515. doi:  10.1038/s41598-017-12984-2
[31] 张忆恒, 杜静, 夏安越, 等. 基于3D打印技术的微芯片用于模拟肠绒毛和肿瘤表面形貌[J]. 上海交通大学学报(医学版), 2019, 39(10):1127-1133.
[32]

DELON L C, GUO Z, OSZMIANA A, et al. A systematic investigation of the effect of the fluid shear stress on Caco-2 cells towards the optimization of epithelial organ-on-chip models[J]. Biomaterials, 2019, 225:119521. doi:  10.1016/j.biomaterials.2019.119521
[33]

TAN H Y, TRIER S, RAHBEK U L, et al. A multi-chamber microfluidic intestinal barrier model using Caco-2 cells for drugtransport studies[J]. PLoS One, 2018, 13(5):e197101.
[34]

KIM H J, HUH D, HAMILTON G, et al. Human gut-on-a-chip inhabited by microbial flora that experiences intestinalperistalsis-like motions and flow[J]. Lab Chip, 2012, 12(12):2165-2174. doi:  10.1039/c2lc40074j
[35]

KIM H J, LI H, COLLINS J J, et al. Contributions of microbiome and mechanical deformation to intestinal bacterialovergrowth and inflammation in a human gut-on-a-chip[J]. Proc Natl Acad Sci U S A, 2016, 113(1):E7-E15.
[36]

JING B, WANG Z A, ZHANG C, et al. Establishment and Application of Peristaltic Human Gut-Vessel Microsystem for Studying Host-Microbial Interaction[J]. Front Bioeng Biotechnol, 2020, 8:272.
[37]

FANG G C, LU H C, AL-NAKASHLI R, et al. Enabling peristalsis of human colon tumor organoids on microfluidic chips[J]. Biofabrication, 2021, 14(1):015006.
[38]

GRASSART A, MALARDÉ V, GOBAA S, et al. Bioengineered Human Organ-on-Chip Reveals Intestinal Microenvironment and Mechanical Forces Impacting Shigella Infection[J]. Cell Host Microbe, 2019, 26(3):435-444. doi:  10.1016/j.chom.2019.08.007
[39]

MARTINEZ-GURYN K, HUBERT N, FRAZIER K, et al. Small Intestine Microbiota Regulate Host Digestive and Absorptive Adaptive Responses to Dietary Lipids[J]. Cell Host Microbe, 2018, 23(4):458-469. doi:  10.1016/j.chom.2018.03.011
[40]

SHIN W, WU A, MASSIDDA M W, et al. A Robust Longitudinal Co-culture of Obligate Anaerobic Gut Microbiome With HumanIntestinal Epithelium in an Anoxic-Oxic Interface-on-a-Chip[J]. Front Bioeng Biotechnol, 2019, 7:13.
[41]

JALILI-FIROOZINEZHAD S, GAZZANIGA F S, CALAMARI E L, et al. A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip[J]. Nat Biomed Eng, 2019, 3(7):520-531. doi:  10.1038/s41551-019-0397-0
[42]

IMURA Y, ASANO Y, SATO K, et al. A microfluidic system to evaluate intestinal absorption[J]. Anal Sci, 2009, 25(12):1403-1407. doi:  10.2116/analsci.25.1403
[43]

JING B, XIA K, ZHANG C, et al. Chitosan Oligosaccharides Regulate the Occurrence and Development of Enteritis ina Human Gut-On-a-Chip[J]. Front Cell Dev Biol, 2022, 10:877892. doi:  10.3389/fcell.2022.877892
[44]

KASENDRA M, TOVAGLIERI A, SONTHEIMER-PHELPS A, et al. Development of a primary human Small Intestine-on-a-Chip using biopsy-derivedorganoids[J]. Sci Rep, 2018, 8(1):2871. doi:  10.1038/s41598-018-21201-7
[45]

KASENDRA M, LUC R, YIN J, et al. Duodenum Intestine-Chip for preclinical drug assessment in a human relevantmodel[J]. Elife, 2020, 9:e50135.
[46]

BEAURIVAGE C, NAUMOVSKA E, CHANG Y X, et al. Development of a Gut-On-A-Chip Model for High Throughput Disease Modeling and Drug Discovery[J]. Int J Mol Sci, 2019, 20(22): 5661.
[47]

GIJZEN L, MARESCOTTI D, RAINERI E, et al. An Intestine-on-a-Chip Model of Plug-and-Play Modularity to Study Inflammatory Processes[J]. SLAS Technol, 2020, 25(6):585-597. doi:  10.1177/2472630320924999
[48]

SHIN W, KIM H J. Intestinal barrier dysfunction orchestrates the onset of inflammatoryhost-microbiome cross-talk in a human gut inflammation-on-a-chip[J]. Proc Natl Acad Sci U S A, 2018, 115(45):E10539-E10547.
[49]

GJOREVSKI N, AVIGNON B, GÉRARD R, et al. Neutrophilic infiltration in organ-on-a-chip model of tissue inflammation[J]. Lab Chip, 2020, 20(18):3365-3374. doi:  10.1039/D0LC00417K
[50]

YEON J H, PARK J K. Drug permeability assay using microhole-trapped cells in a microfluidic device[J]. Anal Chem, 2009, 81(5):1944-1951. doi:  10.1021/ac802351w
[51]

KULTHONG K, DUIVENVOORDE L, SUN H, et al. Microfluidic chip for culturing intestinal epithelial cell layers: Characterization and comparison of drug transport between dynamic and static models[J]. Toxicology in Vitro, 2020, 65:104815. doi:  10.1016/j.tiv.2020.104815
[52]

POCOCK K, DELON L, BALA V, et al. Intestine-on-a-Chip Microfluidic Model for Efficient in Vitro Screening of Oral Chemotherapeutic Uptake[J]. ACS Biomater Sci Eng, 2017, 3(6):951-959.
[53]

Edited by VERHOECKX K, COTTER P, LóPEZ-EXPóSITO I, et al. The Impact of Food Bioactives on Health: in vitro and ex vivo models[M]. Cham (CH): Springer, 2015.
[54]

VAESSEN S F, van LIPZIG M M, PIETERS R H, et al. Regional Expression Levels of Drug Transporters and Metabolizing Enzymes alongthe Pig and Human Intestinal Tract and Comparison with Caco-2 Cells[J]. Drug Metab Dispos, 2017, 45(4):353-360.
[55]

WANG J D, DOUVILLE N J, TAKAYAMA S, et al. Quantitative analysis of molecular absorption into PDMS microfluidic channels[J]. Ann Biomed Eng, 2012, 40(9):1862-1873. doi:  10.1007/s10439-012-0562-z