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Copyright: © 2024 Fofanova et al.Mechanistic 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.
Author(s): Fofanova TY, Karandikar UC, Auchtung JM, Wilson RL, Valentin AJ, Britton RA, Grande-Allen KJ, Estes MK, Hoffman K, Ramani S, Stewart CJ, Petrosino JF
Publication type: Article
Publication status: Published
Journal: PLoS ONE
Year: 2024
Volume: 19
Issue: 7
Print publication date: 25/07/2024
Online publication date: 25/07/2023
Acceptance date: 01/03/2024
Date deposited: 05/08/2024
ISSN (electronic): 1932-6203
Publisher: Public Library of Science
URL: https://doi.org/10.1371/journal.pone.0300666
DOI: 10.1371/journal.pone.0300666
Data Access Statement: All relevant data are within the manuscript and its Supporting Information files.
PubMed id: 39052651
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