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

Ormsby, M. J. et al. (2019) Inflammation associated ethanolamine facilitates infection by Crohn's disease-linked adherent-invasive Escherichia coli. EBioMedicine, 43, pp. 325-332. (doi:10.1016/j.ebiom.2019.03.071) (PMID:31036531) (PMCID:PMC6557746)

[img]
Preview
Text
182792.pdf - Published Version
Available under License Creative Commons Attribution.

860kB

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. Fund: This work was funded by Biotechnology and Biological Sciences Research Council (BBSRC) grants BB/K008005/1 & BB/P003281/1 to DMW; by a Tenovus Scotland grant to MJO; by Glasgow Children's Hospital Charity, Nestle Health Sciences, Engineering and Physical Sciences Research Council (EPSRC) and Catherine McEwan Foundation grants awarded to KG; and by a Natural Environment Research Council (NERC) fellowship (NE/L011956/1) to UZI. The IBD team at the Royal Hospital for Children, Glasgow are supported by the Catherine McEwan Foundation and Yorkhill IBD fund. RKR and RH are supported by NHS Research Scotland Senior fellowship awards.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hansen, Dr Richard and McIntosh, Ms Anne and Russell, Dr Richard and LOGAN, Michael and Fallata, Ghaith and Papadopoulou, Ms Rodanthi and Ormsby, Mr Michael and Johnson, Miss Sile and Wall, Dr Daniel and Gerasimidis, Dr Konstantinos and Ijaz, Dr Umer Zeeshan and Papachristou, Miss Eleftheria
Authors: Ormsby, M. J., Logan, M., Johnson, S. A., McIntosh, A., Fallata, G., Papadopoulou, R., Papachristou, E., Hold, G. L., Hansen, R., Ijaz, U. Z., Russell, R. K., Gerasimidis, K., and Wall, D. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Science and Engineering > School of Engineering
College of Science and Engineering > School of Engineering > Infrastructure and Environment
Journal Name:EBioMedicine
Publisher:Elsevier
ISSN:2352-3964
ISSN (Online):2352-3964
Published Online:26 April 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in EBioMedicine 43: 325-332
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
607841Survival and dissemination of enteric pathogens through exploitation and inhibition of programmed cell death pathways in circulating immune cells.Daniel WallBiotechnology and Biological Sciences Research Council (BBSRC)BB/K008005/1III - BACTERIOLOGY
726481Propionic acid use in agriculture and food production is driving evolution of novel Escherichia coli pathotypesDaniel WallBiotechnology and Biological Sciences Research Council (BBSRC)BB/P003281/1III - BACTERIOLOGY
652772Understanding microbial community through in situ environmental 'omic data synthesisUmer Zeeshan IjazNatural Environment Research Council (NERC)NE/L011956/1ENG - ENGINEERING INFRASTRUCTURE & ENVIR