Intestinal organoid as an in vitro model in studying host-microbial interactions
- 249 Downloads
Organoid is an in vitro three-dimensional organ-bud that shows realistic microanatomy and physiological relevance. The progress in generating organoids that faithfully recapitulate human in vivo tissue composition has extended organoid applications from being just a basic research tool to a translational platform with a wide range of uses. Study of hostmicrobial interactions relies on model systems to mimic the in vivo infection. Researchers have developed various experimental models in vitro and in vivo to examine the dynamic host-microbial interactions. For some infectious pathogens, model systems are lacking whereas some of the used systems are far from optimal.
In the present work, we will review the brief history and recent findings using organoids for studying hostmicrobial interactions.
A systematic literature search was performed using the PubMed search engine. We also shared our data and research contribution to the field.
we summarize the brief history of 3D organoids. We discuss the feasibility of using organoids in studying hostmicrobial interactions, focusing on the development of intestinal organoids and gastric organoids. We highlight the advantage and challenges of the new experimental models. Further, we discuss the future direction in using organoids in studying hostmicrobial interactions and its potential application in biomedical studies.
In combination with genetic, transcriptome and proteomic profiling, both murine- and human-derived organoids have revealed crucial aspects of development, homeostasis and diseases. Specifically, human organoids from susceptible host will be used to test their responses to pathogens, probiotics, and drugs. Organoid system is an exciting tool for studying infectious disease, microbiome, and therapy.
Keywordsbacteria colonoids enteroids gastric organoids host-microbial interactions H. pylori inflammation intestinal organoids microbiome organoids tight junctions Salmonella stem-cell differentiation ZO-1
Unable to display preview. Download preview PDF.
This work was supported by the NIDDK 1R01DK105118-01 and the UIC Cancer Center to Jun Sun.
- Bartfeld S, Bayram T, van de Wetering M, Huch M, Begthel H, Kujala P, Vries R, Peters P J, Clevers H (2015). In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology, 148(1): 126–136.e6Google Scholar
- Bartfeld S, Clevers H (2015). Organoids as model for infectious diseases: Culture of human and murine stomach organoids and microinjection of Helicobacter pylori. J Vis Exp, 43(105):816–818Google Scholar
- Bertaux-Skeirik N, Feng R, Schumacher MA, Li J, MaheMM, Engevik A C, Javier J E, Peek RMJr, Ottemann K, Orian-Rousseau V, Boivin G P, Helmrath M A, Zavros Y (2015). CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation. PLoS Pathog, 11(2): e1004663CrossRefPubMedPubMedCentralGoogle Scholar
- D’Aiuto L, Di Maio R, Heath B, Raimondi G, Milosevic J, Watson A M, Bamne M, Parks WT, Yang L, Lin B, Miki T, Mich-Basso J D, Arav-Boger R, Sibille E, Sabunciyan S, Yolken R, Nimgaonkar V (2012). Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells. PLoS One, 7(11): e49700CrossRefPubMedPubMedCentralGoogle Scholar
- Ettayebi K, Crawford S E, Murakami K, Broughman J R, Karandikar U, Tenge V R, Neill F H, Blutt S E, Zeng X L, Qu L, Kou B, Opekun A R, Burrin D, Graham D Y, Ramani S, Atmar R L, Estes M K (2016). Replication of human noroviruses in stem cell-derived human enteroids. Science, 353(6306): 1387–1393CrossRefPubMedPubMedCentralGoogle Scholar
- Finkbeiner S R, Zeng X L, Utama B, Atmar R L, Shroyer N F, Estes MK (2012). Stem cell-derived human intestinal organoids as an infection model for rotaviruses. MBio, 3(4): e00159–e12Google Scholar
- Forbester J L, Goulding D, et al (2014). Intestinal organoids are a novel system to study Salmonella enterica Serovar Typhimurium interaction with the intestinal epithelial barrier. Immunology, 143: 111–112Google Scholar
- Forbester J L, Goulding D, Vallier L, Hannan N, Hale C, Pickard D, Mukhopadhyay S, Dougan G (2015). Interaction of Salmonella enterica Serovar Typhimurium with intestinal organoids derived from human induced pluripotent stem cells. Infect Immun, 83(7): 2926–2934CrossRefPubMedPubMedCentralGoogle Scholar
- 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, Estes M K, Donowitz M (2014). Human enteroids as an ex-vivo model of hostpathogen interactions in the gastrointestinal tract. Exp Biol Med (Maywood), 239(9): 1124–1134CrossRefGoogle Scholar
- Mahe M M, Sundaram N, Watson C L, Shroyer N F, Helmrath M A (2015). Establishment of human epithelial enteroids and colonoids from whole tissue and biopsy. J Vis Exp, (97): e52483-e52483Google Scholar
- McCracken K W, Catá E M, Crawford C M, Sinagoga K L, Schumacher M, Rockich B E, Tsai Y H, Mayhew C N, Spence J R, Zavros Y, Wells J M (2014). Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature, 516(7531): 400–404CrossRefPubMedPubMedCentralGoogle Scholar
- Penkert R R, Kalejta R F (2013). Human embryonic stem cell lines model experimental human cytomegalovirus latency. MBio, 4(3): e00298–e13Google Scholar
- Sato T, Stange D E, Ferrante M, Vries R G, Van Es J H, Van den Brink S, Van Houdt W J, Pronk A, Van Gorp J, Siersema P D, Clevers H (2011a). Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology, 141(5): 1762–1772CrossRefPubMedGoogle Scholar
- 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, Graham D Y, Qureshi W, Sherman V, Foulke-Abel J, In J, Kovbasnjuk O, Zachos N C, Donowitz M, Estes M K (2015). Human intestinal enteroids: a new model to study human rotavirus infection, host restriction, and pathophysiology. J Virol, 90(1): 43–56CrossRefPubMedPubMedCentralGoogle Scholar
- Schumacher M A, Feng R, Aihara E, Engevik A C, Montrose M H, Ottemann K M, Zavros Y (2015). Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFkB pathway activation: the use of a novel in vitro model to study epithelial response to infection. Helicobacter, 20(1): 19–28CrossRefPubMedGoogle Scholar
- Schwank G, Koo B K, Sasselli V, Dekkers J F, Heo I, Demircan T, Sasaki N, Boymans S, Cuppen E, van der Ent C K, Nieuwenhuis E E, Beekman J M, Clevers H (2013). Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell, 13(6): 653–658CrossRefPubMedGoogle Scholar
- Shlomai A, Schwartz R E, Ramanan V, Bhatta A, de Jong Y P, Bhatia S N, Rice C M (2014). Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems. Proc Natl Acad Sci USA, 111(33): 12193–12198CrossRefPubMedPubMedCentralGoogle Scholar
- Sigal M, RothenbergME, Logan C Y, Lee J Y, Honaker R W, Cooper R L, Passarelli B, Camorlinga M, Bouley D M, Alvarez G, Nusse R, Torres J, Amieva M R (2015). Helicobacter pylori activates and expands Lgr5(+) stem cells through direct colonization of the gastric glands. Gastroenterology, 148(7): 1392–404.e21Google Scholar
- Wang X, Yamamoto Y, Wilson L H, Zhang T, Howitt B E, Farrow M A, Kern F, Ning G, Hong Y, Khor C C, Chevalier B, Bertrand D, Wu L, Nagarajan N, Sylvester F A, Hyams J S, Devers T, Bronson R, Lacy D B, Ho K Y, Crum C P, McKeon F, Xian W (2015). Cloning and variation of ground state intestinal stem cells. Nature, 522(7555): 173–178CrossRefPubMedPubMedCentralGoogle Scholar
- Yin Y, Bijvelds M, Dang W, Xu L, van der Eijk A A, Knipping K, Tuysuz N, Dekkers J F, Wang Y, de Jonge J, Sprengers D, van der Laan L J, Beekman J M, Ten Berge D, Metselaar H J, de Jonge H, Koopmans M P, Peppelenbosch M P, Pan Q (2015). Modeling rotavirus infection and antiviral therapy using primary intestinal organoids. Antiviral Res, 123: 120–131CrossRefPubMedGoogle Scholar
- Yoshida T, Takayama K, Kondoh M, Sakurai F, Tani H, Sakamoto N, Matsuura Y, Mizuguchi H, Yagi K (2011). Use of human hepatocytelike cells derived from induced pluripotent stem cells as a model for hepatocytes in hepatitis C virus infection. Biochem Biophys Res Commun, 416(1–2): 119–124CrossRefPubMedGoogle Scholar