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...
Main Authors: | , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1797320592473456640 |
---|---|
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. |
first_indexed | 2024-03-08T04:41:26Z |
format | Article |
id | doaj.art-ea199dbed44149b295cf6102b0450cc4 |
institution | Directory Open Access Journal |
issn | 1949-0976 1949-0984 |
language | English |
last_indexed | 2024-03-08T04:41:26Z |
publishDate | 2023-12-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | Gut Microbes |
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 |
work_keys_str_mv | AT jettebornholdt detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT christinavmuller detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT mariajuulnielsen detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT jesperstrickertsson detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT dariarago detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT yunchen detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT grzegorzmaciag detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT jonathanskov detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT anjawellejus detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT paweljschweiger detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT stinelhansen detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT christabroholm detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT ismailgogenur detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT marttimaimets detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT stinesloth detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT jakobhendel detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT adambaker detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT albinsandelin detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids AT kimbjensen detectinghostresponsestomicrobialstimulationusingprimaryepithelialorganoids |