Cremer et al.7676. J. Cremer, I. Segota, C. Y. Yang, M. Arnoldini, J. T. Sauls, Z. Zhang, E. Gutierrez, A. Groisman, and T. Hwa, “ Effect of flow and peristaltic mixing on bacterial growth in a gut-like channel,” Proc. Natl. Acad. Sci. U. S. A. 113(41), 11414 (2016). https://doi.org/10.1073/pnas.1601306113The minigut: single minichannel—lumen (microbes)0–50 μm s−1Consecutive valve actuation along the channelAerobicNAE. coli20 hGuo et al.8383. Y. Guo, Z. Li, W. Su, L. Wang, Y. Zhu, and J. Qin, “ A biomimetic human gut-on-a-chip for modeling drug metabolism in intestine,” Artif. Organs 42(12), 1196 (2018). https://doi.org/10.1111/aor.13163Microchannels simulating lumen (with a porous membrane)400 μl h−1NoAerobicCaco-2NA5 days (D) (+12 h drug test)Fois et al.8282. C. A. M. Fois, A. Schindeler, P. Valtchev, and F. Dehghani, “ Dynamic flow and shear stress as key parameters for intestinal cells morphology and polarization in an organ-on-a-chip model,” Biomed. Microdevices 23(4), 55 (2021). https://doi.org/10.1007/s10544-021-00591-ySingle microchannel—lumen29 μl h−1 (Normal)NoAerobicCaco-2 HTB-37™NA8 DChi et al.109109. M. Chi, B. Yi, S. Oh, D. J. Park, J. H. Sung, and S. Park, “ A microfluidic cell culture device (FCCD) to culture epithelial cells with physiological and morphological properties that mimic those of the human intestine,” Biomed. Microdevices 17(3), 9966 (2015). https://doi.org/10.1007/s10544-015-9966-5μFCCD: 2 stacked microchannels—an upper (enterocytes) and a lower channel0.5 μl min−1NoAerobicCaco-2Salmonella enterica S. Typhimurium3 DSecchi et al.8484. E. Secchi, A. Vitale, G. L. Miño, V. Kantsler, L. Eberl, R. Rusconi, and R. Stocker, “ The effect of flow on swimming bacteria controls the initial colonization of curved surfaces,” Nat. Commun. 11(1), 2851 (2020). https://doi.org/10.1038/s41467-020-16620-y,bMicrochannels with pilllars or corrugated topography0.6–6 μl min−1NoAerobicNAP. aeruginosa PA145 hKim et al.8585. M. K. Kim, F. Ingremeau, A. Zhao, B. L. Bassler, and H. A. Stone, “ Local and global consequences of flow on bacterial quorum sensing,” Nat. Microbiol. 1, 15005 (2016). https://doi.org/10.1038/nmicrobiol.2015.5,bMicrochannels with crevices0.1–100 μl min–1NoAerobicNAS. aureus, V. cholerae∼several hours (e.g., up to 30 h)Marzorati et al.8686. M. Marzorati, B. Vanhoecke, T. De Ryck, M. Sadaghian Sadabad, I. Pinheiro, S. Possemiers, P. Van den Abbeele, L. Derycke, M. Bracke, J. Pieters, T. Hennebel, H. J. Harmsen, W. Verstraete, and T. Van de Wiele, “ The HMI™ module: A new tool to study the host-microbiota interaction in the human gastrointestinal tract in vitro,” BMC Microbiol. 14(1), 133 (2014). https://doi.org/10.1186/1471-2180-14-133HMI: two stacked microchannels—lumen (microbes), and host (enterocytes)Lumen: 6.5 ml min−1, host: 2 ml min−1NoAerobic lower chamber and anaerobic upper chamberCaco-2Complex microbial community derived from SHIME® reactors (Lactobacillus rhamnosus GG as the control)7 D human cells, 2 D cocultureShah et al.8787. P. Shah, J. V. Fritz, E. Glaab, M. S. Desai, K. Greenhalgh, A. Frachet, M. Niegowska, M. Estes, C. Jäger, C. Seguin-Devaux, F. Zenhausern, and P. Wilmes, “ A microfluidics-based in vitro model of the gastrointestinal human–microbe interface,” Nat. Commun. 7(1), 11535 (2016). https://doi.org/10.1038/ncomms11535HuMiX: three stacked microchannels—lumen (microbes), human chamber (epithelial), and perfusion chamberLumen: 25 μl min−1, perfusion chamber: 25 μl min−1NoAerobic perfusion chamber and anerobic microbial suspensionCaco-2 or CCD-18Co (human chamber), CD4+ T in the perfusion chambercLactobacillus rhamnosus GG (LGG), Bacteroides caccae7 D human cells, 1 D cocultureKim et al.8888. H. J. Kim, D. Huh, G. Hamilton, and D. E. Ingber, “ Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow,” Lab Chip 12(12), 2165 (2012). https://doi.org/10.1039/c2lc40074jTwo stacked microchannels—lumen (epithelial, microbial cells) and a lower channelBoth channels 30–40 μl h−1Lateral vacuum chambers 10% strain, 0.15 HzAerobicCaco-2Lactobacillus rhamnosus GG (LGG)∼4–5 D human cells, >1 week cocultureKim et al.9494. H. J. Kim, H. Li, J. J. Collins, and D. E. Ingber, “ Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip,” Proc. Natl. Acad. Sci. U. S. A. 113(1), E7 (2016). https://doi.org/10.1073/pnas.1522193112Two stacked microchannels—lumen (epithelial, microbial cells) and vascularLumen: 30 μl h−1, vascular: 30 μl h−1Lateral vacuum chambers 10% strain, 0.15 HzAerobicCaco-2, ±PBMCsA select mixture of gut microbes∼100 h human cells, 72 h cocultureKasendra et al.7171. M. Kasendra, A. Tovaglieri, A. Sontheimer-Phelps, S. Jalili-Firoozinezhad, A. Bein, A. Chalkiadaki, W. Scholl, C. Zhang, H. Rickner, C. A. Richmond, H. Li, D. T. Breault, and D. E. Ingber, “ Development of a primary human small intestine-on-a-chip using biopsy-derived organoids,” Sci. Rep. 8(1), 2871 (2018). https://doi.org/10.1038/s41598-018-21201-7Duodenum intestine-chip: two stacked microchannels—lumen (epithelium) and vascularLumen: 60 μl h−1, vascular: 60 μl h−1Lateral vacuum chambers 10% strain, 0.2 HzAerobicBiopsy-derived organoids (lumen), ±HIMECs (vascular)NA12 DWorkman et al.9393. M. J. Workman, J. P. Gleeson, E. J. Troisi, H. Q. Estrada, S. J. Kerns, C. D. Hinojosa, G. A. Hamilton, S. R. Targan, C. N. Svendsen, and R. J. Barrett, “ Enhanced utilization of induced pluripotent stem cell–derived human intestinal organoids using microengineered chips,” Cell. Mol. Gastroenterol. Hepatol. 5(4), 669 (2018). https://doi.org/10.1016/j.jcmgh.2017.12.008Two stacked microchannels—lumen (epithelium) and vascular30 μl h−1Lateral vacuum chambers 10% strain; 0.2 HzAerobicDissociated organoids generated from induced pluripotent stem cells (CS83iCTR-33n1 and CS688iCTR-n5)NA∼2 WeeksJalili-Firoozinezhad et al.5555. S. Jalili-Firoozinezhad, F. S. Gazzaniga, E. L. Calamari, D. M. Camacho, C. W. Fadel, A. Bein, B. Swenor, B. Nestor, M. J. Cronce, A. Tovaglieri, O. Levy, K. E. Gregory, D. T. Breault, J. M. S. Cabral, D. L. Kasper, R. Novak, and D. E. Ingber, “ A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip,” Nat. Biomed. Eng. 3(7), 520 (2019). https://doi.org/10.1038/s41551-019-0397-0Two stacked microchannels—lumen (epithelium) and vascularLumen: 60 μl h−1, vascular: 60 μl h−1Lateral vacuum chambers 10% cell strain, 0.15 Hz frequency)Anerobic (upper chamber), aerobic (bottom suspension)Human intestinal organoids (lumen), HIMECs (vascular)B. fragilis, human microbiota colonized in mice, microbiota derived from fecal samples∼1 Week human cells, 5D cocultureShim et al.9595. K. Y. Shim, D. Lee, J. Han, N. T. Nguyen, S. Park, and J. H. Sung, “ Microfluidic gut-on-a-chip with three-dimensional villi structure,” Biomed. Microdevices 19(2), 37 (2017). https://doi.org/10.1007/s10544-017-0179-yTwo stacked microchannels—apical and basolateral chambers integrated with a 3D collagen scaffold100 μl min−1NoAerobicCaco-2NA∼14 DShin et al.9696. Y. C. Shin, W. Shin, D. Koh, A. Wu, Y. M. Ambrosini, S. Min, S. G. Eckhardt, R. Y. D. Fleming, S. Kim, S. Park, H. Koh, T. K. Yoo, and H. J. Kim, “ Three-dimensional regeneration of patient-derived intestinal organoid epithelium in a physiodynamic mucosal interface-on-a-chip,” Micromachines 11(7), 663 (2020). https://doi.org/10.3390/mi11070663Two stacked microchannels—lumen and vascular channelsLumen 50 μl h−1, vascular 50 μl h−1Lateral vacuum chambers 5% average elongation at 0.15 HzAnerobic microbial cultureBiopsy-derived organoids from patients with GI diseases (lumen) or Caco-2 cells (lumen)Fecal samples7–10 D human cells, 2 D cocultureJing et al.9797. B. Jing, Z. A. Wang, C. Zhang, Q. Deng, J. Wei, Y. Luo, X. Zhang, J. Li, and Y. Du, “ Establishment and application of peristaltic human gut-vessel microsystem for studying host–microbial interaction,” Front. Bioeng. Biotechnol. 8, 272 (2020). https://doi.org/10.3389/fbioe.2020.00272Three layers, a central lumen and two surrounding vascular channelsVascular: 60 μl h−1, lumen: 0–85 μl h−1Peristaltic flow induced by a pump in the lumen channel (0. 15 Hz)AerobicCaco-2 (lumen), HUVEC (vascular),c macrophages U937 (vascular)cE. coli, L. casei∼5 D human cells, 7 D coculture