Development of a novel human intestinal model to elucidate the effect of anaerobic commensals on Escherichia coli infection

The gut microbiota plays a crucial role in protecting against enteric infection. However, the underlying mechanisms are largely unknown owing to a lack of suitable experimental models. Although most gut commensals are anaerobic, intestinal epithelial cells require oxygen for survival. In addition, m...

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Bibliographic Details
Published in:Disease models & mechanisms 2022-04, Vol.15 (4)
Main Authors: McGrath, Conor J, Laveckis, Edgaras, Bell, Andrew, Crost, Emmanuelle, Juge, Nathalie, Schüller, Stephanie
Format: Article
Language:English
Subjects:
Anaerobiosis
Bacteria
colonization resistance
Diarrhea
Drug resistance
E coli
epec
Epithelial Cells - metabolism
Escherichia coli Infections - metabolism
Escherichia coli Infections - microbiology
Escherichia coli Proteins - metabolism
Experiments
Humans
Infections
intestinal epithelium
Intestinal Mucosa - metabolism
Intestines - microbiology
limosilactobacillus reuteri
Microbiota
model system
mucus
Optimization
Organoids
Pathogens
Proteins
ruminococcus gnavus
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Summary:The gut microbiota plays a crucial role in protecting against enteric infection. However, the underlying mechanisms are largely unknown owing to a lack of suitable experimental models. Although most gut commensals are anaerobic, intestinal epithelial cells require oxygen for survival. In addition, most intestinal cell lines do not produce mucus, which provides a habitat for the microbiota. Here, we have developed a microaerobic, mucus-producing vertical diffusion chamber (VDC) model and determined the influence of Limosilactobacillus reuteri and Ruminococcus gnavus on enteropathogenic Escherichia coli (EPEC) infection. Optimization of the culture medium enabled bacterial growth in the presence of mucus-producing T84/LS174T cells. Whereas L. reuteri diminished EPEC growth and adhesion to T84/LS174T and mucus-deficient T84 epithelia, R. gnavus only demonstrated a protective effect in the presence of LS174T cells. Reduced EPEC adherence was not associated with altered type III secretion pore formation. In addition, co-culture with L. reuteri and R. gnavus dampened EPEC-induced interleukin 8 secretion. The microaerobic mucin-producing VDC system will facilitate investigations into the mechanisms underpinning colonization resistance and aid the development of microbiota-based anti-infection strategies. This article has an associated First Person interview with the first author of the paper.
ISSN:1754-8403
1754-8411
DOI:10.1242/dmm.049365