title: Acute Infectious Gastroenteritis Potentiates a Crohn's Disease Pathobiont to Fuel Ongoing Inflammation in the Post-Infectious Period.
abstract: Crohn's disease (CD) is a chronic inflammatory condition of diverse etiology. Exposure to foodborne pathogens causing acute gastroenteritis produces a long-term risk of CD well into the post-infectious period but the mechanistic basis for this ongoing relationship to disease onset is unknown. We developed two novel models to study the comorbidity of acute gastroenteritis caused by Salmonella Typhimurium or Citrobacter rodentium in mice colonized with adherent-invasive Escherichia coli (AIEC), a bacterial pathobiont linked to CD. Here, we show that disease activity in the post-infectious period after gastroenteritis is driven by the tissue-associated expansion of the resident AIEC pathobiont, with an attendant increase in immunopathology, barrier defects, and delays in mucosal restitution following pathogen clearance. These features required AIEC resistance to host defense peptides and a fulminant inflammatory response to the enteric pathogen. Our results suggest that individuals colonized by AIEC at the time of acute infectious gastroenteritis may be at greater risk for CD onset. Importantly, our data identify AIEC as a tractable disease modifier, a finding that could be exploited in the development of therapeutic interventions following infectious gastroenteritis in at-risk individuals.
authors.affiliation: Michael G. DeGroote Institute for Infectious Disease Research, Hamilton, Ontario, Canada.
authors.forename: Cherrie L
authors.initials: CL
authors.lastname: Small
authors.affiliation: Michael G. DeGroote Institute for Infectious Disease Research, Hamilton, Ontario, Canada.
authors.forename: Lydia
authors.initials: L
authors.lastname: Xing
authors.affiliation: Michael G. DeGroote Institute for Infectious Disease Research, Hamilton, Ontario, Canada.
authors.forename: Joseph B
authors.identifier: http://orcid.org/0000-0002-6844-755X
authors.initials: JB
authors.lastname: McPhee
authors.affiliation: Michael G. DeGroote Institute for Infectious Disease Research, Hamilton, Ontario, Canada.
authors.forename: Hong T
authors.initials: HT
authors.lastname: Law
authors.affiliation: Michael G. DeGroote Institute for Infectious Disease Research, Hamilton, Ontario, Canada.|Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.|Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada.
authors.forename: Brian K
authors.identifier: http://orcid.org/0000-0001-9883-1010
authors.initials: BK
authors.lastname: Coombes
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium; D060085:Coinfection / Q000150:complications*; D003424:Crohn Disease / Q000382:microbiology*; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000150:complications; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000150:complications; D005260:Female; D005759:Gastroenteritis / Q000150:complications*; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000382:microbiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D012481:Salmonella Infections, Animal / Q000150:complications; D012486:Salmonella typhimurium