Neonatal Enteropathogenic Escherichia coli Infection Disrupts Microbiota-Gut-Brain Axis Signaling

Autor: Patricia Stokes, Gonzalo Rabasa, Ingrid Brust-Mascher, Rene Nichols, Mélanie G. Gareau, Mariana Barboza, Carly Hennessey, Trina A. Knotts, Ciara E. Keogh, Matteo M. Pusceddu, Olivia Walsh, Mackenzie Honeycutt, Colin Reardon, Jessica A. Sladek
Přispěvatelé: Brodsky, Igor E
Rok vydání: 2021
Předmět:
Gut flora
Medical and Health Sciences
neuroinflammation
Enteropathogenic Escherichia coli
chemistry.chemical_compound
2.1 Biological and endogenous factors
Aetiology
Fluorescein isothiocyanate
microbiota-gut-brain axis
Escherichia coli Infections
Pediatric
Feedback
Physiological
Host Response and Inflammation
Brain
Biological Sciences
Intestines
neurogenesis
Infectious Diseases
medicine.anatomical_structure
Disease Susceptibility
Infection
medicine.medical_specialty
Physiological
Immunology
Gut–brain axis
Ileum
Biology
digestive system
Microbiology
Feedback
Proinflammatory cytokine
Vaccine Related
Biodefense
Internal medicine
medicine
Animals
Humans
Neuroinflammation
Agricultural and Veterinary Sciences
behavior
Prevention
bacterial infection
Neurosciences
medicine.disease
biology.organism_classification
Gastrointestinal Microbiome
Emerging Infectious Diseases
Endocrinology
chemistry
Parasitology
Digestive Diseases
Dysbiosis
Zdroj: Infect Immun
Infection and immunity, vol 89, iss 9
ISSN: 1098-5522
0019-9567
Popis: 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; ΔescV [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 [I(sc)]) 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 (Tnfα, 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.
Databáze: OpenAIRE
Externí odkaz: