Inflammation associated ethanolamine facilitates infection by Crohn's disease-linked adherent-invasive Escherichia coli

Michael J. Ormsby, Michael Logan, Síle A. Johnson, Anne McIntosh, Ghaith Fallata, Rodanthi Papadopoulou, Eleftheria Papachristou, Georgina L. Hold, Richard Hansen, Umer Z. Ijaz, Richard K. Russell, Konstantinos Gerasimidis, Daniel M. Wall

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Abstract

Background: The predominance of specific bacteria such as adherent-invasive Escherichia coli (AIEC) within the Crohn's disease (CD) intestine remains poorly understood with little evidence uncovered to support a selective pressure underlying their presence. Intestinal ethanolamine is however readily accessible during periods of intestinal inflammation, and enables pathogens to outcompete the host microbiota under such circumstances.

Methods: Quantitative RT-PCR (qRT-PCR) to determine expression of genes central to ethanolamine metabolism; transmission electron microscopy to detect presence of bacterial microcompartments (MCPs); in vitro infections of both murine and human macrophage cell lines examining intracellular replication of the AIEC-type strain LF82 and clinical E. coli isolates in the presence of ethanolamine; determination of E. coli ethanolamine utilization (eut) operon transcription in faecal samples from healthy patients, patients with active CD and the same patients in remission following treatment.

Results: Growth on the intestinal short chain fatty acid propionic acid (PA) stimulates significantly increased transcription of the eut operon (fold change relative to glucose: >16.9; p-value <.01). Additionally ethanolamine was accessible to intra-macrophage AIEC and stimulated significant increases in growth intracellularly when it was added extracellularly at concentrations comparable to those in the human intestine. Finally, qRT-PCR indicated that expression of the E. coli eut operon was increased in children with active CD compared to healthy controls (fold change increase: >4.72; P < .02). After clinical remission post-exclusive enteral nutrition treatment, the same CD patients exhibited significantly reduced eut expression (Pre vs Post fold change decrease: >15.64; P < .01).

Interpretation: Our data indicates a role for ethanolamine metabolism in selecting for AIEC that are consistently overrepresented in the CD intestine. The increased E. coli metabolism of ethanolamine seen in the intestine during active CD, and its decrease during remission, indicates ethanolamine use may be a key factor in shaping the intestinal microbiome in CD patients, particularly during times of inflammation.
Original languageEnglish
Pages (from-to)325-332
Number of pages8
JournalEBioMedicine
Volume43
Early online date26 Apr 2019
DOIs
Publication statusPublished - May 2019

Keywords

  • Ethanolamine
  • Adherent-invasive Escherichia coli
  • Biomarker
  • Crohn's disease

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