Enterohemorrhagic Escherichia coli Reduces Mucus and Intermicrovillar Bridges in Human Stem Cell-Derived Colonoids
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BACKGROUND AND AIMS: (EHEC) causes over 70,000 episodes of foodborne diarrhea annually in the USA. The early sequence of events which precede life-threatening hemorrhagic colitis and hemolytic uremic syndrome are not fully understood due to the initial asymptomatic phase of the disease and the lack of a suitable animal model. The aim of this study was to determine the initial molecular events in the interaction between EHEC and human colonic epithelium. METHODS: Human colonoids derived from adult proximal colonic stem cells were developed into monolayers to study EHEC-epithelial interactions. Monolayer confluency and differentiation were monitored by transepithelial electrical resistance (TER) measurements. The monolayers were apically infected with EHEC and the progression of epithelial damage over time was assessed using biochemical and imaging approaches. RESULTS: Human colonoid cultures recapitulate the differential protein expression patterns characteristic of the crypt and surface colonocytes. Mucus-producing differentiated colonoid monolayers are preferentially colonized by EHEC. Upon colonization, EHEC forms characteristic attaching and effacing lesions on the apical surface of colonoid monolayers. Mucin 2, a main component of colonic mucus, and protocadherin 24 (PCDH24), a microvillar resident protein, are targeted by EHEC at early stages of infection. The EHEC secreted serine protease, EspP, initiates brush border damage through PCDH24 reduction. CONCLUSIONS: Human colonoid monolayers are a relevant pathophysiological model which allows the study of early molecular events during enteric infections. Colonoid monolayers provide access to both apical and basolateral surfaces, thus providing an advantage over 3D cultures to study host-pathogen interactions in a controllable and tractable manner. EHEC reduces colonic mucus and affects the brush border cytoskeleton in the absence of commensal bacteria.
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Organoid-derived 2D monolayer culture models have been instrumental for studies in which access to the apical surface is important.
“Furthermore, the recent development of organoid-derived 2D monolayer culture models has been instrumental for studies in which access to the apical surface is important [10,11,44].”
From Regulation of Enterocyte Brush Border Membrane Primary Na-Absorptive Transporters in Human Intestinal Organoid-Derived Monolayers (2024) · cites this paper as [44]
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Cites
One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products.
Datsenko, K., & Wanner, B. (2000) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.120163297 · Cited by 15,902 · see citing works
Kaper, J. B., Nataro, J. P., & Mobley, H. L. T. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro818 · Cited by 5,583 · see citing works
Self-citationSato, T., Stange, D. E., Ferrante, M., Vries, R. G. J., van Es, J. H., van den Brink, S., van Houdt, W. J., Pronk, A., van Gorp, J., Siersema, P. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.050 · Cited by 3,753 · see citing works
Organoid Models and Applications in Biomedical Research
Xinaris, C., Brizi, V., & Remuzzi, G. (2015) · The Nephron journals/Nephron journals · doi:10.1159/000433566 · Cited by 3,517 · see citing works
The gastrointestinal mucus system in health and disease
Johansson, M. E. V., Sjövall, H., & Hansson, G. C. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.35 · Cited by 1,438 · see citing works
Molecular mechanisms of Escherichia coli pathogenicity
Croxen, M. A., & Finlay, B. B. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2265 · Cited by 1,222 · see citing works
Origins of the E. coli Strain Causing an Outbreak of Hemolytic–Uremic Syndrome in Germany
Rasko, D. A., Webster, D. R., Sahl, J. W., Bashir, A., Boisen, N., Scheutz, F., Paxinos, E. E., Sebra, R., Chin, C.-S., Iliopoulos, D., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1106920 · Cited by 825 · see citing works
Isolation and in vitro expansion of human colonic stem cells
Jung, P., Sato, T., Merlos-Suárez, A., Barriga, F. M., Iglesias, M., Rossell, D., Auer, H., Gallardo, M., Blasco, M. A., Sancho, E., et al. (2011) · Nature Medicine · doi:10.1038/nm.2470 · Cited by 709 · see citing works
Kosinski, C., Li, V. S. W., Chan, A. S. Y., Zhang, J., Ho, C., Tsui, W. Y., Chan, T. L., Mifflin, R. C., Powell, D. W., Yuen, S. T., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707210104 · Cited by 596 · see citing works
Verocytotoxin-producing Escherichia coli (VTEC)
Karmali, M. A., Gannon, V. P. J., & Sargeant, J. M. (2009) · Veterinary Microbiology · doi:10.1016/j.vetmic.2009.04.011 · Cited by 543 · see citing works
VanDussen, K. L., Marinshaw, J. M., Shaikh, N., Miyoshi, H., Moon, C., Tarr, P. I., Ciorba, M. A., & Stappenbeck, T. S. (2015) · Gut · doi:10.1136/gutjnl-2013-306651 · Cited by 525 · see citing works
Fucose sensing regulates bacterial intestinal colonization
Pacheco, A. R., Curtis, M. M., Ritchie, J. M., Munera, D., Waldor, M. K., Moreira, C. G., & Sperandio, V. (2012) · Nature · doi:10.1038/nature11623 · Cited by 499 · see citing works
Ermund, A., Schutte, A. H., Johansson, M., Gustafsson, J. K., & Hansson, G. C. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00046.2013 · Cited by 392 · see citing works
Enterohemorrhagic E. coli (EHEC) pathogenesis
Nguyen, Y., & Sperandio, V. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00090 · Cited by 315 · see citing works
Rendón, M. A., Saldaña‐Ahuactzi, Z., Erdem, A. L., Monteiro‐Neto, V., Vázquez, A., Kaper, J. B., Puente, J. L., & Girón, J. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704104104 · Cited by 305 · see citing works
Self-citationHeijmans, J., van Lidth de Jeude, J. F., Koo, B.-K., Rosekrans, S. L., Wielenga, M. C. B., van de Wetering, M., Ferrante, M., Lee, A. S., Onderwater, J. J. M., Paton, J. C., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.02.031 · Cited by 293 · see citing works
Prominin-1/CD133 Marks Stem Cells and Early Progenitors in Mouse Small Intestine
Snippert, H. J. G., van Es, J. H., van den Born, M., Begthel, H., Stange, D. E., Barker, N., & Clevers, H. C. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.03.002 · Cited by 215 · see citing works
The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer
Kovbasnjuk, O. N., Mourtazina, R., Baibakov, B. A., Wang, T., Elowsky, C. G., Choti, M. A., Kane, A. V., & Donowitz, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506474102 · Cited by 194 · see citing works
Self-citationIntestinal Brush Border Assembly Driven by Protocadherin-Based Intermicrovillar Adhesion
Crawley, S. W., Shifrin, D. A., Grega‐Larson, N. E., McConnell, R. E., Benesh, A. E., Mao, S., Zheng, Y., Zheng, Q. Y., Nam, K. T., Millis, B. A., et al. (2014) · Cell · doi:10.1016/j.cell.2014.01.067 · Cited by 186 · see citing works
Foulke-Abel, J., In, J., Kovbasnjuk, O., Zachos, N. C., Ettayebi, K., Blutt, S. E., Hyser, J. M., Zeng, X.-L., Crawford, S. E., Broughman, J. R., et al. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214529398 · Cited by 179 · see citing works
Self-citationErdem, A. L., Avelino, F., Xicohtencatl‐Cortés, J., & Girón, J. A. (2007) · Journal of Bacteriology · doi:10.1128/jb.00464-07 · Cited by 174 · see citing works
Shiga toxin in enterohemorrhagic E.coli: regulation and novel anti-virulence strategies
Pacheco, A. R., & Sperandio, V. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00081 · Cited by 165 · see citing works
Mouse Models of Escherichia coli O157:H7 Infection and Shiga Toxin Injection
Mohawk, K. L., & O’Brien, A. D. (2011) · BioMed Research International · doi:10.1155/2011/258185 · Cited by 164 · see citing works
Enteropathogenic E. coli disrupts tight junction barrier function and structure in vivo
Shifflett, D. E., Clayburgh, D. R., Koutsouris, A., Turner, J. R., & Hecht, G. A. (2005) · Laboratory Investigation · doi:10.1038/labinvest.3700330 · Cited by 150 · see citing works
Human Response to Escherichia coli O157:H7 Infection: Antibodies to Secreted Virulence Factors
Li, Y., Frey, E. A., Mackenzie, A. M. R., & Finlay, B. B. (2000) · Infection and Immunity · doi:10.1128/iai.68.9.5090-5095.2000 · Cited by 140 · see citing works
Grys, T. E., Siegel, M. B., Lathem, W. W., & Welch, R. A. (2005) · Infection and Immunity · doi:10.1128/iai.73.3.1295-1303.2005 · Cited by 138 · see citing works
An unusual signal peptide facilitates late steps in the biogenesis of a bacterial autotransporter
Szabady, R. L., Peterson, J. H., Skillman, K. M., & Bernstein, H. D. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406055102 · Cited by 137 · see citing works
Self-citationTreatment of enterohemorrhagic Escherichia coli (EHEC) infection and hemolytic uremic syndrome (HUS)
Goldwater, P. N., & Bettelheim, K. A. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-12 · Cited by 123 · see citing works
代替指標としてCD8 + 細胞におけるローダミン123蓄積を用いる,In vivo塩酸セファランチンのP糖蛋白質調節作用の研究
Li, H., Zhang, Y., Wang, N., Guo, X., Zang, C.-H., Jiang, J., Ma, F., & Wang, Q. (2011) · BioMed Research International · Cited by 119 · see citing works
Roxas, J. L., Koutsouris, A., Bellmeyer, A., Tesfay, S., Royan, S. V., Falzari, K., Harris, A., Cheng, H., Rhee, K. J., & Hecht, G. A. (2010) · Laboratory Investigation · doi:10.1038/labinvest.2010.91 · Cited by 114 · see citing works
Donohue‐Rolfe, A., Kondova, I. I., Oswald, S., Hutto, D., & Tzipori, S. R. (2000) · The Journal of Infectious Diseases · doi:10.1086/315421 · Cited by 96 · see citing works
Sjogren, R. W., Neill, R. J., Rachmilewitz, D., Fritz, D., Newland, J. W., Sharpnack, D. D., Colleton, C. A., Fondacaro, J. D., Gemski, P., & Boedeker, E. C. (1994) · Gastroenterology · doi:10.1016/0016-5085(94)90587-8 · Cited by 73 · see citing works
Bertin, Y., Chaucheyras‐Durand, F., Masselot, C. R., Durand, A., Foye, A. D. L., Harel, J., Cohen, P. S., Conway, T., Forano, É., & Martin, C. (2012) · Environmental Microbiology · doi:10.1111/1462-2920.12019 · Cited by 72 · see citing works
Enterohemorrhagic Escherichia coli Colonization of Human Colonic Epithelium In Vitro and Ex Vivo
Lewis, S. B., Cook, V., Tighe, R., & Schüller, S. (2014) · Infection and Immunity · doi:10.1128/iai.02928-14 · Cited by 65 · see citing works
Brockmeyer, J., Bielaszewska, M., Fruth, A., Bonn, M. L., Mellmann, A., Humpf, H., & Karch, H. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.00920-07 · Cited by 60 · see citing works
Characterization of the StcE Protease Activity of <i>Escherichia coli</i> O157:H7
Grys, T. E., Walters, L. L., & Welch, R. A. (2006) · Journal of Bacteriology · doi:10.1128/jb.01806-05 · Cited by 51 · cited 1× · see citing works
“However, StcE was shown to specifically target orally expressed MUC7,(29) and its role in the reduction of MUC2-positive mucus in nontransformed human colonic epithelial cells is unknown.(29) Therefore, we tested whether StcE contributes to EHECinduced reduction of the MUC2-positive mucus layer in HCM.”
BackgroundMunera, D., Ritchie, J. M., Hatzios, S. K., Bronson, R. T., Fang, G., Schadt, E. E., Davis, B. M., & Waldor, M. K. (2014) · Nature Communications · doi:10.1038/ncomms4080 · Cited by 44 · see citing works
Boisen, N., Hansen, A., Melton‐Celsa, A. R., Zangari, T., Mortensen, N. P., Kaper, J. B., O’Brien, A. D., & Nataro, J. P. (2014) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiu399 · Cited by 40 · see citing works
Self-citationLukyanenko, V. I., Malyukova, I. V., Hubbard, A. L., Delannoy, M. R., Boedeker, E. C., Zhu, C., Cebotaru, L., & Kovbasnjuk, O. N. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00036.2011 · Cited by 40 · see citing works
Self-citationIn, J., Lukyanenko, V. I., Foulke-Abel, J. D., Hubbard, A. L., Delannoy, M. R., Hansen, A., Kaper, J. B., Boisen, N., Nataro, J. P., Zhu, C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069196 · Cited by 26 · see citing works
Self-citationPrevalence, Biogenesis, and Functionality of the Serine Protease Autotransporter EspP
Weiss, A., & Brockmeyer, J. (2012) · Toxins · doi:10.3390/toxins5010025 · Cited by 22 · see citing works
Yashunsky, V., Kharilker, L., Zlotkin‐Rivkin, E., Rund, D., Melamed‐Book, N., Zahavi, E. E., Perlson, E., Mercone, S., Golosovsky, M., Davidov, D., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078431 · Cited by 8 · see citing works
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- [36]Bertin Y. Chaucheyras-Durand F. Robbe-Masselot C. Carbohydrate utilization by enterohaemorrhagic Escherichia coli O157:H7 in bovine intestinal content Environ Microbiol 15 2013 610 622 23126484 PMC3558604
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The intestinal epithelial barrier: a therapeutic target?
Odenwald, M. A., & Turner, J. R. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.169 · Cited by 1,288 · see citing works
Martinez-Guryn, K., Hubert, N., Frazier, K., Urlass, S., Musch, M. W., Ojeda, P., Pierre, J. F., Miyoshi, J., Sontag, T. J., Cham, C. M., et al. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.03.011 · Cited by 663 · see citing works
Gut Microbiota and Colonization Resistance against Bacterial Enteric Infection
Ducarmon, Q. R., Zwittink, R. D., Hornung, B. V. H., van Schaik, W., Young, V. B., & Kuijper, E. J. (2019) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00007-19 · Cited by 566 · see citing works
Human organoids in basic research and clinical applications
Tang, X.-Y., Wu, S., Wang, D., Chu, C., Hong, Y., Tao, M., Hu, H., Xu, M., Guo, X. L., & Liu, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01024-9 · Cited by 509 · see citing works
Nakamoto, N., Sasaki, N., Aoki, R., Miyamoto, K., Suda, W., Teratani, T., Suzuki, T., Koda, Y., Chu, P.-S., Taniki, N., et al. (2019) · Nature Microbiology · doi:10.1038/s41564-018-0333-1 · Cited by 425 · see citing works
Noel, G., Baetz, N. W., Staab, J. F., Donowitz, M., Kovbasnjuk, O., Pasetti, M. F., & Zachos, N. C. (2017) · Scientific Reports · doi:10.1038/srep45270 · Cited by 420 · see citing works
Self-citationModelling Cryptosporidium infection in human small intestinal and lung organoids
Heo, I., Dutta, D., Schaefer, D. A., Iakobachvili, N., Artegiani, B., Sachs, N., Boonekamp, K. E., Bowden, G. D., Hendrickx, A. P. A., Willems, R. J. L., et al. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0177-8 · Cited by 386 · see citing works
Saxena, K., Blutt, S. E., Ettayebi, K., Zeng, X.-L., Broughman, J. R., Crawford, S. E., Karandikar, U. C., Sastri, N. P., Conner, M. E., Opekun, A. R., et al. (2016) · Journal of Virology · doi:10.1128/jvi.01930-15 · Cited by 375 · see citing works
Self-citationGut Microbiota and Intestinal Trans-Epithelial Permeability
Allam‐Ndoul, B., Castonguay-Paradis, S., & Veilleux, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176402 · Cited by 356 · see citing works
Rawat, M., Nighot, M., Al–Sadi, R., Gupta, Y. A., Viszwapriya, D., Yochum, G. S., Koltun, W. A., & Ma, T. Y. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.06.038 · Cited by 268 · see citing works
The mucosal barrier at a glance
France, M. M., & Turner, J. R. (2017) · Journal of Cell Science · doi:10.1242/jcs.193482 · Cited by 268 · see citing works
Williamson, I., Arnold, J. W., Samsa, L. A., Gaynor, L. T., DiSalvo, M., Cocchiaro, J. L., Carroll, I. M., Azcárate-Peril, M. A., Rawls, J. F., Allbritton, N. L., et al. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.05.004 · Cited by 248 · see citing works
Sontheimer-Phelps, A., Chou, D. B., Tovaglieri, A., Ferrante, T. C., Duckworth, T., Fadel, C., Frismantas, V., Sutherland, A. D., Jalili-Firoozinezhad, S., Kasendra, M., et al. (2020) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2019.11.008 · Cited by 239 · see citing works
Mucus models to evaluate the diffusion of drugs and particles
Lock, J. Y., Carlson, T. L., & Carrier, R. L. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.11.001 · Cited by 249 · see citing works
Co, J. Y., Margalef-Català, M., Monack, D. M., & Amieva, M. R. (2021) · Nature Protocols · doi:10.1038/s41596-021-00607-0 · Cited by 236 · see citing works
Organoids and organs-on-chips: Insights into human gut-microbe interactions
Puschhof, J., Pleguezuelos‐Manzano, C., & Clevers, H. C. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2021.04.002 · Cited by 226 · see citing works
Self-renewing Monolayer of Primary Colonic or Rectal Epithelial Cells
Wang, Y., DiSalvo, M., Gunasekara, D. B., Dutton, J. S., Proctor, A., Lebhar, M. S., Williamson, I., Speer, J. E., Howard, R. L., Smiddy, N. M., et al. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.02.011 · Cited by 200 · see citing works
Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology
Foulke-Abel, J. D., In, J., Yin, J., Zachos, N. C., Kovbasnjuk, O. N., Estes, M. K., de Jonge, H. R., & Donowitz, M. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.11.047 · Cited by 194 · see citing works
Self-citationDevelopment and Characterization of a Human and Mouse Intestinal Epithelial Cell Monolayer Platform
Kozuka, K., He, Y., Koo-McCoy, S., Kumaraswamy, P., Nie, B., Shaw, K., Chan, P., Leadbetter, M., He, L., Lewis, J. G., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.10.013 · Cited by 179 · see citing works
Experimental models to study intestinal microbes–mucus interactions in health and disease
Etienne‐Mesmin, L., Chassaing, B., Desvaux, M., Paepe, K. D., Gresse, R., Sauvaitre, T., Forano, É., de Wiele, T. V., Schüller, S., Juge, N., et al. (2019) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuz013 · Cited by 179 · see citing works
Somatic cell-derived organoids as prototypes of human epithelial tissues and diseases
Fujii, M., & Sato, T. (2020) · Nature Materials · doi:10.1038/s41563-020-0754-0 · Cited by 165 · see citing works
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Pearce, S., Coia, H. G., Karl, J. P., Pantoja-Feliciano, I. G., Zachos, N. C., & Racicot, K. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01584 · Cited by 159 · see citing works
Self-citationKarve, S. S., Pradhan, S. K., Ward, D. V., & Weiss, A. A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0178966 · Cited by 157 · see citing works
Barrila, J., Crabbé, A., Yang, J., Franco, K., Nydam, S. D., Forsyth, R. J., Davis, R. R., Gangaraju, S., Ott, C. M., Coyne, C. B., et al. (2018) · Infection and Immunity · doi:10.1128/iai.00282-18 · Cited by 159 · see citing works
Gut organoids: mini-tissues in culture to study intestinal physiology and disease
Almeqdadi, M., Mana, M., Roper, J., & Yilmaz, Ö. H. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00300.2017 · Cited by 151 · see citing works
van der Hee, B., Loonen, L. M. P., Taverne, N., Taverne-Thiele, J. J., Smidt, H., & Wells, J. M. (2018) · Stem Cell Research · doi:10.1016/j.scr.2018.02.013 · Cited by 144 · see citing works
Gastrointestinal tract modeling using organoids engineered with cellular and microbiota niches
Min, S., Kim, S., & Cho, S. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0386-0 · Cited by 145 · see citing works
Translational applications of adult stem cell-derived organoids
Drost, J., & Clevers, H. C. (2017) · Development · doi:10.1242/dev.140566 · Cited by 141 · see citing works
Primary Cell-Derived Intestinal Models: Recapitulating Physiology
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Mechanisms of Intestinal Epithelial Barrier Dysfunction by Adherent-Invasive Escherichia coli
Shawki, A., & McCole, D. F. (2016) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.10.004 · Cited by 133 · see citing works
Altay, G., Larrañaga, E., Tosi, S., Barriga, F. M., Batlle, E., Fernández‐Majada, V., & Martínez, E. (2019) · Scientific Reports · doi:10.1038/s41598-019-46497-x · Cited by 132 · see citing works
Human mini-guts: New insights into intestinal physiology and host–pathogen interactions
In, J. G., Foulke-Abel, J., Estes, M. K., Zachos, N. C., Kovbasnjuk, O., & Donowitz, M. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.142 · Cited by 125 · see citing works
Self-citationSaxena, K., Simon, L. M., Zeng, X., Blutt, S. E., Crawford, S. E., Sastri, N. P., Karandikar, U. C., Ajami, N. J., Zachos, N. C., Kovbasnjuk, O. N., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1615422114 · Cited by 120 · see citing works
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Evaluating Shigella flexneri Pathogenesis in the Human Enteroid Model
Ranganathan, S., Doucet, M., Grassel, C. L., Delaine-Elias, B., Zachos, N. C., & Barry, E. M. (2019) · Infection and Immunity · doi:10.1128/iai.00740-18 · Cited by 105 · see citing works
Self-citationIntestinal organoids: A new paradigm for engineering intestinal epithelium in vitro
Rahmani, S., Breyner, N. M., Su, H.-M., Verdu, E. F., & Didar, T. F. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2018.12.006 · Cited by 98 · see citing works
The Past, Present and Future of Intestinal In Vitro Cell Systems for Drug Absorption Studies
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The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update
Azar, J. H., Bahmad, H. F., Daher, D., Moubarak, M. M., Hadadeh, O., Monzer, A., Bitar, S. A., Jamal, M., Al‐Sayegh, M., & Abou-Kheir, W. G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147667 · Cited by 101 · see citing works
Biologically inspired approaches to enhance human organoid complexity
Holloway, E. M., Capeling, M. M., & Spence, J. R. (2019) · Development · doi:10.1242/dev.166173 · Cited by 96 · see citing works
Silberger, D. J., Zindl, C., & Weaver, C. T. (2017) · Mucosal Immunology · doi:10.1038/mi.2017.47 · Cited by 87 · see citing works
Copper Transport and Disease: What Can We Learn from Organoids?
Pierson, H. E., Yang, H., & Lutsenko, S. (2019) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082018-124242 · Cited by 93 · see citing works
Wang, B. X., Wheeler, K. M., Cady, K. C., Lehoux, S. D., Cummings, R. D., Laub, M. T., & Ribbeck, K. (2020) · Current Biology · doi:10.1016/j.cub.2020.09.088 · Cited by 92 · see citing works
Gastrointestinal Organoids: Understanding the Molecular Basis of the Host–Microbe Interface
Hill, D. R., & Spence, J. R. (2016) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.11.007 · Cited by 87 · see citing works
Organoid-based Models to Study the Role of Host-microbiota Interactions in IBD
Poletti, M., Arnauts, K., Ferrante, M., & Korcsmáros, T. (2020) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjaa257 · Cited by 87 · see citing works
Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell Function
Singh, V., Johnson, K. F., Yin, J., Lee, S., Lin, R., Yu, H. M., In, J., Foulke-Abel, J. D., Zachos, N. C., Donowitz, M., et al. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.08.010 · Cited by 88 · see citing works
Self-citationEngineered Human Gastrointestinal Cultures to Study the Microbiome and Infectious Diseases
Blutt, S. E., Crawford, S. E., Ramani, S., Zou, W. Y., & Estes, M. K. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.12.001 · Cited by 83 · see citing works
Self-citationBein, A., Fadel, C. W., Swenor, B., Cao, W., Powers, R. K., Camacho, D. M., Naziripour, A., Parsons, A., LoGrande, N., Sanjay, S. T., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00899-x · Cited by 80 · see citing works
Rajan, A., Vela, L., Zeng, X., Yu, X., Shroyer, N. F., Blutt, S. E., Poole, N. M., Carlin, L. G., Nataro, J. P., Estes, M. K., et al. (2018) · mBio · doi:10.1128/mbio.02419-17 · Cited by 81 · see citing works
Self-citationOrganoid Models for Infectious Disease
Blutt, S. E., & Estes, M. K. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-042320-023055 · Cited by 78 · see citing works
Self-citation3D bioengineered tissue model of the large intestine to study inflammatory bowel disease
Roh, T. T., Chen, Y., Paul, H. T., Guo, C., & Kaplan, D. L. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119517 · Cited by 79 · see citing works
Applications of human organoids in the personalized treatment for digestive diseases
Wang, Q., Guo, F., Jin, Y., & Ma, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01194-6 · Cited by 82 · see citing works
Hews, C. L., Tran, S.-L., Wegmann, U., Brett, B., Walsham, A. D. S., Kavanaugh, D., Ward, N. J., Juge, N., & Schüller, S. (2017) · Cellular Microbiology · doi:10.1111/cmi.12717 · Cited by 77 · see citing works
Allaire, J. M., Morampudi, V., Crowley, S. M., Stahl, M., Yu, H., Bhullar, K., Knodler, L. A., Bressler, B. L., Jacobson, K., & Vallance, B. A. (2018) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00181.2017 · Cited by 75 · see citing works
Organoid and Enteroid Modeling of Salmonella Infection
Yin, Y., & Zhou, D. (2018) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2018.00102 · Cited by 74 · see citing works
Bovine colon organoids: From 3D bioprinting to cryopreserved multi-well screening platforms
Töpfer, E., Pasotti, A., Telopoulou, A., Italiani, P., Boraschi, D., Ewart, M., & Wilde, C. J. (2019) · Toxicology in Vitro · doi:10.1016/j.tiv.2019.104606 · Cited by 73 · see citing works
Coculture of primary human colon monolayer with human gut bacteria
Zhang, J., Hernandez‐Gordillo, V., Trapečar, M., Wright, C. W., Taketani, M., Schneider, K., Chen, W. L. K., Stas, E., Breault, D. T., Carrier, R. L., et al. (2021) · Nature Protocols · doi:10.1038/s41596-021-00562-w · Cited by 72 · see citing works
Intestinal enteroids/organoids: A novel platform for drug discovery in inflammatory bowel diseases
Yoo, J. H., & Donowitz, M. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i30.4125 · Cited by 72 · see citing works
Self-citationBioengineered Systems and Designer Matrices That Recapitulate the Intestinal Stem Cell Niche
Wang, Y., Kim, R., Hinman, S. S., Zwarycz, B., Magness, S. T., & Allbritton, N. L. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.01.008 · Cited by 70 · see citing works
Ambrosini, Y. M., Park, Y., Jergens, A. E., Shin, W., Min, S., Atherly, T. A., Borcherding, D. C., Jang, J., Allenspach, K., Mochel, J. P., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0231423 · Cited by 68 · see citing works
Hinman, S. S., Wang, Y., Kim, R., & Allbritton, N. L. (2020) · Nature Protocols · doi:10.1038/s41596-020-00419-8 · Cited by 64 · see citing works
Co‐Culture System of Human Enteroids/Colonoids with Innate Immune Cells
Staab, J. F., Lemme‐Dumit, J. M., Latanich, R., Pasetti, M. F., & Zachos, N. C. (2020) · Current Protocols in Immunology · doi:10.1002/cpim.113 · Cited by 68 · see citing works
Self-citationApostolou, A. P., Panchakshari, R. A., Banerjee, A., Manatakis, D. V., Paraskevopoulou, M. D., Luc, R., Abu-Ali, G., Dimitriou, A., Lucchesi, C., Kulkarni, G., et al. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.07.004 · Cited by 66 · see citing works
Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers
Ventayol, P. S., Geiser, P., Martino, M. L. D., Florbrant, A., Fattinger, S. A., Walder, N., Sima, E., Shao, F., Gekara, N. O., Sundbom, M., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2013963118 · Cited by 65 · see citing works
Epigenetic Changes Induced by Bacteroides fragilis Toxin
Allen, J., Hao, S., Sears, C., & Timp, W. (2018) · Infection and Immunity · doi:10.1128/iai.00447-18 · Cited by 65 · see citing works
Creating a More Perfect Union: Modeling Intestinal Bacteria-Epithelial Interactions Using Organoids
Han, X., Mslati, M. A., Davies, E., Chen, Y., Allaire, J. M., & Vallance, B. A. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.04.010 · Cited by 60 · see citing works
Wang, Y., Kim, R., Sims, C. E., & Allbritton, N. L. (2019) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2019.07.009 · Cited by 62 · see citing works
Advances in modelling the human microbiome–gut–brain axis in vitro
Moysidou, C., & Owens, R. M. (2021) · Biochemical Society Transactions · doi:10.1042/bst20200338 · Cited by 60 · see citing works
In vitro models to study human gut-microbiota interactions: Applications, advances, and limitations
Qi, Y., Yu, L., Tian, F., Zhao, J., & Zhai, Q. (2023) · Microbiological Research · doi:10.1016/j.micres.2023.127336 · Cited by 61 · see citing works
Enterotoxigenic Escherichia coli–blood group A interactions intensify diarrheal severity
Kumar, P., Kuhlmann, F., Chakraborty, S., Bourgeois, A. L., Foulke-Abel, J. D., Tumala, B., Vickers, T. J., Sack, D. A., DeNearing, B., Harro, C. D., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97659 · Cited by 59 · see citing works
Self-citationPoole, N. M., Green, S. I., Rajan, A., Vela, L. E., Zeng, X., Estes, M. K., & Maresso, A. W. (2017) · Infection and Immunity · doi:10.1128/iai.00581-17 · Cited by 58 · see citing works
Self-citationYin, J., Tse, C.-M., Avula, L. R., Singh, V., Foulke-Abel, J., de Jonge, H. R., & Donowitz, M. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.02.002 · Cited by 58 · see citing works
Self-citationCarvalho, I., Silva, N. A., Carrola, J. S., SILVA, V. Y. N. E. D., Currie, C., Igrejas, G., & Poeta, P. A. C. Q. D. (2019) · doi:10.1002/9781119282549.ch11 · Cited by 58 · see citing works
Cassotta, M., Forbes-Hernández, T. Y., Iglesias, R. C., Ruíz, R., Elexpuru-Zabaleta, M., Giampieri, F., & Battino, M. A. (2020) · Nutrients · doi:10.3390/nu12061827 · Cited by 58 · see citing works
Mucus layer modeling of human colonoids during infection with enteroaggragative E. coli
Liu, L., Saitz, W., Smith, R., Gonyar, L. A., In, J., Kovbasnjuk, O. N., Zachos, N. C., Donowitz, M., Nataro, J. P., & Ruı́z-Pérez, F. (2020) · Scientific Reports · doi:10.1038/s41598-020-67104-4 · Cited by 57 · see citing works
Self-citationYouhanna, S. C., Kemas, A. M., Preiss, L. C., Zhou, Y., Shen, J. X., Cakal, S. D., Paqualini, F. S., Goparaju, S. K., Shafagh, R. Z., Lind, J. U., et al. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000238 · Cited by 57 · see citing works
Rapid Prototyping of Multilayer Microphysiological Systems
Hosic, S., Bindas, A. J., Puzan, M. L., Lake, W., Soucy, J. R., Zhou, F., Koppes, R. A., Breault, D. T., Murthy, S. K., & Koppes, A. N. (2020) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.0c00190 · Cited by 52 · see citing works
Fernando, E. H., Dicay, M. S., Stahl, M., Gordon, M., Vegso, A. J., Baggio, C. H., Alston, L. A., Lopes, F., Baker, K., Hirota, S. A., et al. (2017) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00152.2017 · Cited by 54 · see citing works
Jubelin, G., Desvaux, M., Schüller, S., Etienne‐Mesmin, L., Muniesa, M., & Blanquet‐Diot, S. (2018) · Microorganisms · doi:10.3390/microorganisms6040115 · Cited by 54 · see citing works
Microbe–Mucus Interface in the Pathogenesis of Colorectal Cancer
Coleman, O. I., & Haller, D. (2021) · Cancers · doi:10.3390/cancers13040616 · Cited by 54 · see citing works
Tse, C.-M., Yin, J., Singh, V., Sarker, R., Lin, R., Verkman, A. S., Turner, J. R., & Donowitz, M. (2019) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2019.01.002 · Cited by 53 · see citing works
Self-citationGut-on-a-Chip Models: Current and Future Perspectives for Host–Microbial Interactions Research
Morelli, M., Kurek, D., Ng, C. P., & Queiroz, K. C. S. (2023) · Biomedicines · doi:10.3390/biomedicines11020619 · Cited by 53 · see citing works
Alpha-defensin-dependent enhancement of enteric viral infection
Wilson, S. S., Bromme, B. A., Holly, M. K., Wiens, M. E., Gounder, A. P., Sul, Y., & Smith, J. G. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006446 · Cited by 52 · see citing works
Impact of dietary fibers in infant formulas on gut microbiota and the intestinal immune barrier
Kong, C., Faas, M. M., de Vos, P., & Akkerman, R. (2020) · Food & Function · doi:10.1039/d0fo01700k · Cited by 51 · see citing works
Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function
Schreiber, F., Balas, I., Robinson, M. J., & Bakdash, G. (2024) · Cells · doi:10.3390/cells13060477 · Cited by 54 · see citing works
Physiologically relevant human tissue models for infectious diseases
Mills, M., & Estes, M. K. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.06.020 · Cited by 50 · see citing works
Self-citationThe Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology
Yu, H. M., Hasan, N. M., In, J., Estes, M. K., Kovbasnjuk, O. N., Zachos, N. C., & Donowitz, M. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105211 · Cited by 49 · see citing works
Self-citationMini-gut: a promising model for drug development
Yin, Y., de Jonge, H. R., Wu, X., & Yin, Y. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.06.006 · Cited by 49 · see citing works
Potential Use of Human Stem Cell-Derived Intestinal Organoids to Study Inflammatory Bowel Diseases.
Dotti, I., & Salas, A. (2018) · Europe PMC (PubMed Central) · doi:10.1093/ibd/izy275 · Cited by 48 · see citing works
Bioengineered Co-culture of organoids to recapitulate host-microbe interactions
Kim, M. B., Hwangbo, S., Jang, S., & Jo, Y. K. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100345 · Cited by 47 · see citing works
Fluid shear stress enhances differentiation of jejunal human enteroids in Intestine-Chip
Yin, J., Sunuwar, L., Kasendra, M. J., Yu, H. M., Tse, C., Talbot, C. C., Boronina, T. N., Cole, R. N., Karalis, K., & Donowitz, M. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00282.2020 · Cited by 46 · see citing works
Self-citationEverything You Always Wanted to Know About Organoid-Based Models (and Never Dared to Ask)
Hautefort, I., Poletti, M., Papp, D., & Korcsmaros, T. D. (2022) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2022.04.012 · Cited by 46 · see citing works
Modeling Intestinal Stem Cell Function with Organoids
Takahashi, T., Fujishima, K., & Kengaku, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222010912 · Cited by 45 · see citing works
In, J., Foulke-Abel, J. D., Clarke, E., & Kovbasnjuk, O. N. (2019) · Journal of Visualized Experiments · doi:10.3791/59357 · Cited by 44 · see citing works
Self-citationWang, Y., Kim, R., Hwang, S.-H. J., Dutton, J. S., Sims, C. E., & Allbritton, N. L. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b02835 · Cited by 40 · see citing works
Brush border protocadherin CDHR2 promotes the elongation and maximized packing of microvilli in vivo
Pinette, J. A., Mao, S., Millis, B. A., Krystofiak, E., Faust, J. J., & Tyska, M. J. (2018) · Molecular Biology of the Cell · doi:10.1091/mbc.e18-09-0558 · Cited by 40 · see citing works
Roles of the Cell Surface Architecture of Bacteroides and Bifidobacterium in the Gut Colonization
Nishiyama, K., Yokoi, T., Sugiyama, M., Osawa, R., Mukai, T., & Okada, N. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.754819 · Cited by 40 · see citing works
Ranganathan, S., Smith, E. M., Foulke-Abel, J. D., & Barry, E. M. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1795389 · Cited by 39 · see citing works
Self-citationGastrointestinal microphysiological systems
Blutt, S. E., Broughman, J. R., Zou, W. Y., Zeng, X., Karandikar, U. C., In, J., Zachos, N. C., Kovbasnjuk, O. N., Donowitz, M., & Estes, M. K. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217710638 · Cited by 40 · see citing works
Self-citationRecent progress in organoid culture to model intestinal epithelial barrier functions
Nakamura, T. (2018) · International Immunology · doi:10.1093/intimm/dxy065 · Cited by 35 · see citing works
Rajan, A., Robertson, M. J., Carter, H. E., Poole, N. M., Clark, J. R., Green, S. I., Criss, Z. K., Zhao, B., Karandikar, U. C., Xing, Y., et al. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008851 · Cited by 38 · see citing works
Self-citation
- Authors
- In, J., Foulke-Abel, J., Zachos, N. C., Hansen, A.-M., Kaper, J. B., Bernstein, H. D., Halushka, M., Blutt, S., Estes, M. K., Donowitz, M., & Kovbasnjuk, O.
- Affiliations
- Johns Hopkins University (US)
- University of Maryland, Baltimore (US)
- National Institutes of Health (US)
- Baylor College of Medicine (US)
- Corresponding author
- Kovbasnjuk, Olga
- ORCID
- Venue
- Cellular and Molecular Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 2
- Issue
- 1
- Pages
- 48-62.e3
- ISSN
- 2352-345X (ISSN-L)
- PMC
- PMC4740923
- OpenAlex
- W2193652497
- Cited by
- 239
- References
- 42
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 24 · 2023: 22 · 2022: 30 · 2021: 28 · 2020: 34 · 2019: 30 · 2018: 23 · 2017: 22 · 2016: 6 · 2015: 3
- FWCI
- 14.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cellular and Molecular Gastroenterology and Hepatology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Johns Hopkins University
- National Institutes of Health (5r24dk064388-07, U18TR000552)
- National Institute of Allergy and Infectious Diseases (U19AI116497)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007632, P30DK089502, R24DK-064388, P01DK072084, R01DK026523, R24DK099803)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Enterobacteriaceae and Cronobacter Research
- Keywords
- enterohemorrhagic Escherichia coli, colonoids, mucus production, MUC2, attaching and effacing lesions, host-pathogen interaction, transepithelial electrical resistance
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