Neonatal enteropathogenic escherichia coli infection disrupts microbiota-gut-brain axis signaling

Carly Hennessey, Ciara E. Keogh, Mariana Barboza, Ingrid Brust-Mascher, Trina A. Knotts, Jessica A. Sladek, Matteo M. Pusceddu, Patricia Stokes, Gonzalo Rabasa, Mackenzie Honeycutt, Olivia Walsh, Rene Nichols, Colin Reardon, Mélanie G. Gareau

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Diarrheal diseases are a leading cause of death in children under the age of 5 years worldwide. Repeated early-life exposures to diarrheal pathogens can result in comorbidities including stunted growth and cognitive deficits, suggesting an impairment in the microbiota-gut-brain (MGB) axis. Neonatal C57BL/6 mice were infected with enteropathogenic Escherichia coli (EPEC) (strain e2348/69; DescV [type III secretion system {T3SS} mutant]) or the vehicle (Luria-Bertani [LB] broth) via orogastric gavage at postnatal day 7 (P7). Behavior (novel-object recognition [NOR] task, light/dark [L/D] box, and open-field test [OFT]), intestinal physiology (Ussing chambers), and the gut microbiota (16S Illumina sequencing) were assessed in adulthood (6 to 8 weeks of age). Neonatal infection of mice with EPEC, but not the T3SS mutant, caused ileal inflammation in neonates and impaired recognition memory (NOR task) in adulthood. Cognitive impairments were coupled with increased neurogenesis (Ki67 and doublecortin immunostaining) and neuroinflammation (increased microglia activation [Iba1]) in adulthood. Intestinal pathophysiology in adult mice was characterized by increased secretory state (short-circuit current [Isc]) and permeability (conductance) (fluorescein isothiocyanate [FITC]-dextran flux) in the ileum and colon of neonatally EPEC-infected mice, along with increased expression of proinflammatory cytokines (Tnfa, Il12, and Il6) and pattern recognition receptors (Nod1/2 and Tlr2/4). Finally, neonatal EPEC infection caused significant dysbiosis of the gut microbiota, including decreased Firmicutes, in adulthood. Together, these findings demonstrate that infection in early life can significantly impair the MGB axis in adulthood.

Original languageEnglish (US)
Article numbere00059-21
JournalInfection and immunity
Volume89
Issue number9
DOIs
StatePublished - Sep 2021

Keywords

  • Bacterial infection
  • Behavior
  • Microbiota-gut-brain axis
  • Neurogenesis
  • Neuroinflammation

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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