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PMID: 30120269 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

AIEC infection triggers modification of gut microbiota composition in genetically predisposed mice, contributing to intestinal inflammation.

Scientific reports ·Vol. 8 ·No. 1 ·2018-00-17 ·Pages 12301

Bretin A, Lucas C, Larabi A, Dalmasso G, Billard E, Barnich N, Bonnet R, Nguyen HTT

Abstract

A high prevalence of adherent-invasive E. coli (AIEC) in the intestinal mucosa of Crohn's disease patients has been shown. AIEC colonize the intestine and induce inflammation in genetically predisposed mouse models including CEABAC10 transgenic (Tg) mice expressing human CEACAM6-receptor for AIEC and eif2ak4-/- mice exhibiting autophagy defect in response to AIEC infection. Here, we aimed at investigating whether gut microbiota modification contributes to AIEC-induced intestinal inflammation in these mouse models. For this, eif2ak4+/+ and eif2ak4-/- mice or CEABAC10 Tg mice invalidated for Eif2ak4 gene (Tg/eif2ak4-/-) or not (Tg/eif2ak4+/+) were infected with the AIEC reference strain LF82 or the non-pathogenic E. coli K12 MG1655 strain. In all mouse groups, LF82 colonized the gut better and longer than MG1655. No difference in fecal microbiota composition was observed in eif2ak4+/+ and eif2ak4-/- mice before infection and at day 1 and 4 post-infection. LF82-infected eif2ak4-/- mice exhibited altered fecal microbiota composition at day 14 and 21 post-infection and increased fecal lipocalin-2 level at day 21 post-infection compared to other groups, indicating that intestinal inflammation developed after microbiota modification. Similar results were obtained for LF82-infected Tg/eif2ak4-/- mice. These results suggest that in genetically predisposed hosts, AIEC colonization might induce chronic intestinal inflammation by altering the gut microbiota composition.

MeSH Terms
Animals Escherichia coli/genetics,physiology Escherichia coli K12/genetics,isolation & purification Female Gastrointestinal Microbiome/genetics,physiology Intestines/immunology Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Protein Serine-Threonine Kinases/deficiency,genetics
Chemicals
Eif2ak4 protein, mouse Protein Serine-Threonine Kinases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Bretin Alexis
M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France.
Lucas Cécily
M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France.
Larabi Anaïs
M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France.
Dalmasso Guillaume ORCID
M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France.
Billard Elisabeth
M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France.
Barnich Nicolas
M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France.
Bonnet Richard
M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France. | Centre Hospitalier Universitaire (CHU), Clermont-Ferrand, 63001, France.
Nguyen Hang Thi Thu
M2iSH (Microbes, intestine, inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRA USC 2018, Clermont-Ferrand, 63001, France. hang.nguyen@uca.fr.
References (53)
53 references, click to expand
  1. Mucosal flora in inflammatory bowel disease.
    Gastroenterology. 2002 Jan;122(1):44-54 PMID: 11781279
  2. Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease.
    Nat Genet. 2008 Oct;40(10):1211-5 PMID: 18758464
  3. Changes in human fecal microbiota due to chemotherapy analyzed by TaqMan-PCR, 454 sequencing and PCR-DGGE fingerprinting.
    PLoS One. 2011;6(12):e28654 PMID: 22194876
  4. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB.
    Appl Environ Microbiol. 2006 Jul;72(7):5069-72 PMID: 16820507
  5. A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes.
    Gastroenterology. 2010 Dec;139(6):1844-1854.e1 PMID: 20816835
  6. Differences between tissue-associated intestinal microfloras of patients with Crohn's disease and ulcerative colitis.
    J Clin Microbiol. 2006 Nov;44(11):4136-41 PMID: 16988016
  7. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease.
    J Clin Invest. 2007 Jun;117(6):1566-74 PMID: 17525800
  8. Molecular diversity of Escherichia coli in the human gut: new ecological evidence supporting the role of adherent-invasive E. coli (AIEC) in Crohn's disease.
    Inflamm Bowel Dis. 2009 Jun;15(6):872-82 PMID: 19235912
  9. Infectious etiopathogenesis of Crohn's disease.
    World J Gastroenterol. 2014 Sep 14;20(34):12102-17 PMID: 25232246
  10. Crohn's disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM.
    J Exp Med. 2009 Sep 28;206(10):2179-89 PMID: 19737864
  11. Regulated translation initiation controls stress-induced gene expression in mammalian cells.
    Mol Cell. 2000 Nov;6(5):1099-108 PMID: 11106749
  12. Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease.
    Gut. 2006 Dec;55(12):1760-7 PMID: 16648155
  13. Metagenomic analysis of the human distal gut microbiome.
    Science. 2006 Jun 2;312(5778):1355-9 PMID: 16741115
  14. Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly.
    Cell Microbiol. 2010 Jan;12(1):99-113 PMID: 19747213
  15. The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation.
    Nature. 2016 Mar 24;531(7595):523-527 PMID: 26982722
  16. AIEC pathobiont instigates chronic colitis in susceptible hosts by altering microbiota composition.
    Gut. 2014 Jul;63(7):1069-80 PMID: 23896971
  17. Crohn's disease-associated adherent invasive Escherichia coli modulate levels of microRNAs in intestinal epithelial cells to reduce autophagy.
    Gastroenterology. 2014 Feb;146(2):508-19 PMID: 24148619
  18. The genetics of Crohn's disease and ulcerative colitis--status quo and beyond.
    Scand J Gastroenterol. 2015 Jan;50(1):13-23 PMID: 25523552
  19. Use of Germ-Free Animal Models in Microbiota-Related Research.
    J Microbiol Biotechnol. 2015 Oct;25(10):1583-8 PMID: 26032361
  20. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach.
    Gut. 2006 Feb;55(2):205-11 PMID: 16188921
  21. Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease.
    Gastroenterology. 1998 Dec;115(6):1405-13 PMID: 9834268
  22. Fecal lipocalin 2, a sensitive and broadly dynamic non-invasive biomarker for intestinal inflammation.
    PLoS One. 2012;7(9):e44328 PMID: 22957064
  23. Functional characterisation of decoy receptor 3 in Crohn's disease.
    Gut. 2009 Apr;58(4):483-91 PMID: 19039087
  24. Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation.
    Gut. 2014 Jan;63(1):116-24 PMID: 23598352
  25. The gut microbiota shapes intestinal immune responses during health and disease.
    Nat Rev Immunol. 2009 May;9(5):313-23 PMID: 19343057
  26. The ATG16L1-T300A allele impairs clearance of pathosymbionts in the inflamed ileal mucosa of Crohn's disease patients.
    Gut. 2015 Oct;64(10):1546-52 PMID: 25253126
  27. Function of the microbiota.
    Best Pract Res Clin Gastroenterol. 2013 Feb;27(1):5-16 PMID: 23768548
  28. Invasive Escherichia coli are a feature of Crohn's disease.
    Lab Invest. 2007 Oct;87(10):1042-54 PMID: 17660846
  29. Bacteriophages Targeting Adherent Invasive Escherichia coli Strains as a Promising New Treatment for Crohn's Disease.
    J Crohns Colitis. 2017 Jul 1;11(7):840-847 PMID: 28130329
  30. Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation.
    Sci Rep. 2016 Jan 08;6:19032 PMID: 26742586
  31. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease.
    Gastroenterology. 2004 Aug;127(2):412-21 PMID: 15300573
  32. Nutrient sensing and metabolic stress pathways in innate immunity.
    Cell Microbiol. 2013 Oct;15(10):1632-41 PMID: 23834352
  33. Changes in the bacterial flora of the neoterminal ileum after ileocolonic resection for Crohn's disease.
    Am J Gastroenterol. 2002 Apr;97(4):939-46 PMID: 12003430
  34. The resilience of the intestinal microbiota influences health and disease.
    Nat Rev Microbiol. 2017 Oct;15(10):630-638 PMID: 28626231
  35. Acute dextran sulfate sodium (DSS)-induced colitis promotes gut microbial dysbiosis in mice.
    J Basic Microbiol. 2016 Sep;56(9):986-98 PMID: 27112251
  36. Activation of the EIF2AK4-EIF2A/eIF2α-ATF4 pathway triggers autophagy response to Crohn disease-associated adherent-invasive Escherichia coli infection.
    Autophagy. 2016 May 3;12(5):770-83 PMID: 26986695
  37. Enhanced Escherichia coli adherence and invasion in Crohn's disease and colon cancer.
    Gastroenterology. 2004 Jul;127(1):80-93 PMID: 15236175
  38. Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum.
    ISME J. 2007 Sep;1(5):403-18 PMID: 18043660
  39. Antibiotic exposure and IBD development among children: a population-based cohort study.
    Pediatrics. 2012 Oct;130(4):e794-803 PMID: 23008454
  40. Fungal microbiota dysbiosis in IBD.
    Gut. 2017 Jun;66(6):1039-1048 PMID: 26843508
  41. Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence.
    Gut. 2016 Feb;65(2):225-37 PMID: 25887379
  42. Altered gut microbiota composition in immune-impaired Nod2(-/-) mice.
    Gut. 2012 Apr;61(4):634-5 PMID: 21868489
  43. Nod2 is essential for temporal development of intestinal microbial communities.
    Gut. 2011 Oct;60(10):1354-62 PMID: 21421666
  44. High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease.
    Gut. 2007 May;56(5):669-75 PMID: 17028128
  45. A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease.
    PLoS One. 2013 Nov 19;8(11):e80702 PMID: 24260458
  46. Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases.
    Cell Host Microbe. 2008 Jun 12;3(6):417-27 PMID: 18541218
  47. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases.
    Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13780-5 PMID: 17699621
  48. Practical Considerations and the Intestinal Microbiome in Disease: Antibiotics for IBD Therapy.
    Dig Dis. 2016;34(1-2):112-21 PMID: 26982586
  49. Adherent invasive Escherichia coli strains from patients with Crohn's disease survive and replicate within macrophages without inducing host cell death.
    Infect Immun. 2001 Sep;69(9):5529-37 PMID: 11500426
  50. Autophagy and Crohn's disease.
    J Innate Immun. 2013;5(5):434-43 PMID: 23328432
  51. Defects in autophagy favour adherent-invasive Escherichia coli persistence within macrophages leading to increased pro-inflammatory response.
    Cell Microbiol. 2012 Jun;14(6):791-807 PMID: 22309232
  52. Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample.
    Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4516-22 PMID: 20534432
  53. Culture-independent analyses of temporal variation of the dominant fecal microbiota and targeted bacterial subgroups in Crohn's disease.
    J Clin Microbiol. 2006 Nov;44(11):3980-8 PMID: 16988018
Article Info
Journal
Scientific reports
Abbr.
Sci Rep
ISSN
2045-2322
DOI
10.1038/s41598-018-30055-y
Email
hang.nguyen@uca.fr
Published
2018-00-17
Epub
2018-00-17
Pages
12301
Language
English
Region
England
NLM ID
101563288
PMCID
PMC6098085
Subset
IM
External Links
PubMed source DOI: 10.1038/s41598-018-30055-y PMC Full Text View journal details
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