Detecting host responses to microbial stimulation using primary epithelial organoids

ABSTRACTThe intestinal epithelium is constantly exposed to microbes residing in the lumen. Traditionally, the response to microbial interactions has been studied in cell lines derived from cancerous tissues, e.g. Caco-2. It is, however, unclear how the responses in these cancer cell lines reflect th...

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Main Authors: Jette Bornholdt, Christina V. Müller, Maria Juul Nielsen, Jesper Strickertsson, Daria Rago, Yun Chen, Grzegorz Maciag, Jonathan Skov, Anja Wellejus, Pawel J. Schweiger, Stine L. Hansen, Christa Broholm, Ismail Gögenur, Martti Maimets, Stine Sloth, Jakob Hendel, Adam Baker, Albin Sandelin, Kim B. Jensen
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Gut Microbes
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2023.2281012
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author Jette Bornholdt
Christina V. Müller
Maria Juul Nielsen
Jesper Strickertsson
Daria Rago
Yun Chen
Grzegorz Maciag
Jonathan Skov
Anja Wellejus
Pawel J. Schweiger
Stine L. Hansen
Christa Broholm
Ismail Gögenur
Martti Maimets
Stine Sloth
Jakob Hendel
Adam Baker
Albin Sandelin
Kim B. Jensen
author_facet Jette Bornholdt
Christina V. Müller
Maria Juul Nielsen
Jesper Strickertsson
Daria Rago
Yun Chen
Grzegorz Maciag
Jonathan Skov
Anja Wellejus
Pawel J. Schweiger
Stine L. Hansen
Christa Broholm
Ismail Gögenur
Martti Maimets
Stine Sloth
Jakob Hendel
Adam Baker
Albin Sandelin
Kim B. Jensen
author_sort Jette Bornholdt
collection DOAJ
description ABSTRACTThe intestinal epithelium is constantly exposed to microbes residing in the lumen. Traditionally, the response to microbial interactions has been studied in cell lines derived from cancerous tissues, e.g. Caco-2. It is, however, unclear how the responses in these cancer cell lines reflect the responses of a normal epithelium and whether there might be microbial strain-specific effects. To address these questions, we derived organoids from the small intestine from a cohort of healthy individuals. Culturing intestinal epithelium on a flat laminin matrix induced their differentiation, facilitating analysis of microbial responses via the apical membrane normally exposed to the luminal content. Here, it was evident that the healthy epithelium across multiple individuals (n = 9) demonstrates robust acute both common and strain-specific responses to a range of probiotic bacterial strains (BB-12Ⓡ, LGGⓇ, DSM33361, and Bif195). Importantly, parallel experiments using the Caco-2 cell line provide no acute response. Collectively, we demonstrate that primary epithelial cells maintained as organoids represent a valuable resource for assessing interactions between the epithelium and luminal microbes across individuals, and that these models are likely to contribute to a better understanding of host microbe interactions.
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spelling doaj.art-ea199dbed44149b295cf6102b0450cc42024-02-08T12:02:08ZengTaylor & Francis GroupGut Microbes1949-09761949-09842023-12-0115210.1080/19490976.2023.2281012Detecting host responses to microbial stimulation using primary epithelial organoidsJette Bornholdt0Christina V. Müller1Maria Juul Nielsen2Jesper Strickertsson3Daria Rago4Yun Chen5Grzegorz Maciag6Jonathan Skov7Anja Wellejus8Pawel J. Schweiger9Stine L. Hansen10Christa Broholm11Ismail Gögenur12Martti Maimets13Stine Sloth14Jakob Hendel15Adam Baker16Albin Sandelin17Kim B. Jensen18Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkHuman Health Research, Chr. Hansen AS, Hørsholm, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, DenmarkHuman Health Research, Chr. Hansen AS, Hørsholm, DenmarkNovo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, DenmarkHuman Health Research, Chr. Hansen AS, Hørsholm, DenmarkCenter for Surgical Science, Department of Surgery, Zealand University Hospital, Koge, DenmarkNovo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, DenmarkDepartment of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, DenmarkDepartment of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, DenmarkHuman Health Research, Chr. Hansen AS, Hørsholm, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkABSTRACTThe intestinal epithelium is constantly exposed to microbes residing in the lumen. Traditionally, the response to microbial interactions has been studied in cell lines derived from cancerous tissues, e.g. Caco-2. It is, however, unclear how the responses in these cancer cell lines reflect the responses of a normal epithelium and whether there might be microbial strain-specific effects. To address these questions, we derived organoids from the small intestine from a cohort of healthy individuals. Culturing intestinal epithelium on a flat laminin matrix induced their differentiation, facilitating analysis of microbial responses via the apical membrane normally exposed to the luminal content. Here, it was evident that the healthy epithelium across multiple individuals (n = 9) demonstrates robust acute both common and strain-specific responses to a range of probiotic bacterial strains (BB-12Ⓡ, LGGⓇ, DSM33361, and Bif195). Importantly, parallel experiments using the Caco-2 cell line provide no acute response. Collectively, we demonstrate that primary epithelial cells maintained as organoids represent a valuable resource for assessing interactions between the epithelium and luminal microbes across individuals, and that these models are likely to contribute to a better understanding of host microbe interactions.https://www.tandfonline.com/doi/10.1080/19490976.2023.2281012Intestinal organoidsprobioticsmicrobiomeintestinal epitheliumbacterial–epithelial interactions
spellingShingle Jette Bornholdt
Christina V. Müller
Maria Juul Nielsen
Jesper Strickertsson
Daria Rago
Yun Chen
Grzegorz Maciag
Jonathan Skov
Anja Wellejus
Pawel J. Schweiger
Stine L. Hansen
Christa Broholm
Ismail Gögenur
Martti Maimets
Stine Sloth
Jakob Hendel
Adam Baker
Albin Sandelin
Kim B. Jensen
Detecting host responses to microbial stimulation using primary epithelial organoids
Gut Microbes
Intestinal organoids
probiotics
microbiome
intestinal epithelium
bacterial–epithelial interactions
title Detecting host responses to microbial stimulation using primary epithelial organoids
title_full Detecting host responses to microbial stimulation using primary epithelial organoids
title_fullStr Detecting host responses to microbial stimulation using primary epithelial organoids
title_full_unstemmed Detecting host responses to microbial stimulation using primary epithelial organoids
title_short Detecting host responses to microbial stimulation using primary epithelial organoids
title_sort detecting host responses to microbial stimulation using primary epithelial organoids
topic Intestinal organoids
probiotics
microbiome
intestinal epithelium
bacterial–epithelial interactions
url https://www.tandfonline.com/doi/10.1080/19490976.2023.2281012
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