Journal
EBIOMEDICINE
Volume 43, Issue -, Pages 325-332Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2019.03.071
Keywords
Ethanolamine; Adherent-invasive Escherichia coli; Biomarker; Crohn's disease
Funding
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/K008005/1, BB/P003281/1]
- Tenovus Scotland grant
- Glasgow Children's Hospital Charity
- Engineering and Physical Sciences Research Council (EPSRC)
- Catherine McEwan Foundation
- Natural Environment Research Council (NERC) [NE/L011956/1]
- Yorkhill IBD fund
- NHS Research Scotland Senior fellowship awards
- Nestle Health Sciences
- BBSRC [BB/P003281/1, BB/K008005/1] Funding Source: UKRI
- NERC [NE/L011956/1] Funding Source: UKRI
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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 arid 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-exdusive 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. (C) 2019 Published by Elsevier B.V.
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