A novel system to culture human intestinal organoids under physiological oxygen content to study microbial-host interaction

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dc.citation.articleNumbere0300666en_US
dc.citation.issueNumber7en_US
dc.citation.journalTitlePLOS ONEen_US
dc.citation.volumeNumber19en_US
dc.contributor.authorFofanova, Tatiana Y.en_US
dc.contributor.authorKarandikar, Umesh C.en_US
dc.contributor.authorAuchtung, Jennifer M.en_US
dc.contributor.authorWilson, Reid L.en_US
dc.contributor.authorValentin, Antonio J.en_US
dc.contributor.authorBritton, Robert A.en_US
dc.contributor.authorGrande-Allen, K. Janeen_US
dc.contributor.authorEstes, Mary K.en_US
dc.contributor.authorHoffman, Kristien_US
dc.contributor.authorRamani, Sashirekhaen_US
dc.contributor.authorStewart, Christopher J.en_US
dc.contributor.authorPetrosino, Joseph F.en_US
dc.date.accessioned2024-08-09T16:25:25Zen_US
dc.date.available2024-08-09T16:25:25Zen_US
dc.date.issued2024en_US
dc.description.abstractMechanistic investigation of host-microbe interactions in the human gut are hindered by difficulty of co-culturing microbes with intestinal epithelial cells. On one hand the gut bacteria are a mix of facultative, aerotolerant or obligate anaerobes, while the intestinal epithelium requires oxygen for growth and function. Thus, a coculture system that can recreate these contrasting oxygen requirements is critical step towards our understanding microbial-host interactions in the human gut. Here, we demonstrate Intestinal Organoid Physoxic Coculture (IOPC) system, a simple and cost-effective method for coculturing anaerobic intestinal bacteria with human intestinal organoids (HIOs). Using commensal anaerobes with varying degrees of oxygen tolerance, such as nano-aerobe Bacteroides thetaiotaomicron and strict anaerobe Blautia sp., we demonstrate that IOPC can successfully support 24–48 hours HIO-microbe coculture. The IOPC recapitulates the contrasting oxygen conditions across the intestinal epithelium seen in vivo. The IOPC cultured HIOs showed increased barrier integrity, and induced expression of immunomodulatory genes. A transcriptomic analysis suggests that HIOs from different donors show differences in the magnitude of their response to coculture with anaerobic bacteria. Thus, the IOPC system provides a robust coculture setup for investigating host-microbe interactions in complex, patient-derived intestinal tissues, that can facilitate the study of mechanisms underlying the role of the microbiome in health and disease.en_US
dc.identifier.citationFofanova, T. Y., Karandikar, U. C., Auchtung, J. M., Wilson, R. L., Valentin, A. J., Britton, R. A., Grande-Allen, K. J., Estes, M. K., Hoffman, K., Ramani, S., Stewart, C. J., & Petrosino, J. F. (2024). A novel system to culture human intestinal organoids under physiological oxygen content to study microbial-host interaction. PLOS ONE, 19(7), e0300666. https://doi.org/10.1371/journal.pone.0300666en_US
dc.identifier.digitaljournal-pone-0300666en_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0300666en_US
dc.identifier.urihttps://hdl.handle.net/1911/117636en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleA novel system to culture human intestinal organoids under physiological oxygen content to study microbial-host interactionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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