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Publication
Neonatal Enteropathogenic Escherichia coli Infection Disrupts
Microbiota-Gut-Brain Axis Signaling.
Authors Hennessey C, Keogh CE, Barboza M, Brust-Mascher I, Knotts TA, Sladek JA,
Pusceddu MM, Stokes P, Rabasa G, Honeycutt M, Walsh O, Nichols R, Reardon C,
Gareau MG
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Infection and immunity
Year 2021
Date Published 8/1/2021
Volume : Pages 89 : e0005921
PubMed Reference 33820817
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; ?escV
[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.




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