{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hennessey C"],"funding":["HHS | NIH | National Institute of Mental Health","NICHD NIH HHS","HHS | NIH | National Center for Complementary and Integrative Health","NCCIH NIH HHS","HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","NIDDK NIH HHS","NIAID NIH HHS","NIMH NIH HHS","HHS | NIH | National Institute of Allergy and Infectious Diseases"],"pagination":["e0005921"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8370682"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["89(9)"],"pubmed_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; Δ<i>escV</i> [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>I</i><sub>sc</sub>]) 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 (<i>Tnf</i>α, <i>Il12</i>, and <i>Il6</i>) and pattern recognition receptors (<i>Nod1/2</i> and <i>Tlr2/4</i>). Finally, neonatal EPEC infection caused significant dysbiosis of the gut microbiota, including decreased <i>Firmicutes</i>, in adulthood. Together, these findings demonstrate that infection in early life can significantly impair the MGB axis in adulthood."],"journal":["Infection and immunity"],"pubmed_title":["Neonatal Enteropathogenic Escherichia coli Infection Disrupts Microbiota-Gut-Brain Axis Signaling."],"pmcid":["PMC8370682"],"funding_grant_id":["P50 HD103526","T32AI060555","R21 MH108154","U24-DK092993","P50HD103526","T32 AI060555","U24 DK092993","R01 AT009365","1R21MH108154-01","U2C DK092993","1R01AT009365-01"],"pubmed_authors":["Gareau MG","Sladek JA","Rabasa G","Brust-Mascher I","Stokes P","Honeycutt M","Knotts TA","Walsh O","Nichols R","Pusceddu MM","Hennessey C","Barboza M","Keogh CE","Reardon C"],"additional_accession":[]},"is_claimable":false,"name":"Neonatal Enteropathogenic Escherichia coli Infection Disrupts Microbiota-Gut-Brain Axis Signaling.","description":"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; Δ<i>escV</i> [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>I</i><sub>sc</sub>]) 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 (<i>Tnf</i>α, <i>Il12</i>, and <i>Il6</i>) and pattern recognition receptors (<i>Nod1/2</i> and <i>Tlr2/4</i>). Finally, neonatal EPEC infection caused significant dysbiosis of the gut microbiota, including decreased <i>Firmicutes</i>, in adulthood. Together, these findings demonstrate that infection in early life can significantly impair the MGB axis in adulthood.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Aug","modification":"2026-06-12T09:07:14.801Z","creation":"2025-04-06T14:07:47.893Z"},"accession":"S-EPMC8370682","cross_references":{"pubmed":["33820817"],"doi":["10.1128/IAI.00059-21","10.1128/iai.00059-21"]}}