title: Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior.
abstract: There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood-brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria.
authors.affiliation: McMaster Brain-Body Institute at St Joseph's Healthcare Hamilton, 50 Charlton Avenue East T3304, Hamilton, Ontario, Canada L8N 4A6.|Department of Pathology and Molecular Medicine, McMaster University, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6.
authors.forename: Sophie
authors.initials: S
authors.lastname: Leclercq
authors.affiliation: McMaster Brain-Body Institute at St Joseph's Healthcare Hamilton, 50 Charlton Avenue East T3304, Hamilton, Ontario, Canada L8N 4A6.
authors.forename: Firoz M
authors.initials: FM
authors.lastname: Mian
authors.affiliation: McMaster Brain-Body Institute at St Joseph's Healthcare Hamilton, 50 Charlton Avenue East T3304, Hamilton, Ontario, Canada L8N 4A6.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Stanisz
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Avenue E. Mounier 73, Brussels 1200, Belgium.
authors.forename: Laure B
authors.identifier: 0000-0003-3747-3234
authors.initials: LB
authors.lastname: Bindels
authors.affiliation: Faculty of Medicine, Université Catholique de Louvain, Brussels 1200, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Cambier
authors.affiliation: Faculty of Medicine, Bar-Ilan University, Henrietta Szold 8, Safed 1311502, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Ben-Amram
authors.affiliation: Faculty of Medicine, Bar-Ilan University, Henrietta Szold 8, Safed 1311502, Israel.
authors.forename: Omry
authors.identifier: 0000-0002-7738-1337
authors.initials: O
authors.lastname: Koren
authors.affiliation: McMaster Brain-Body Institute at St Joseph's Healthcare Hamilton, 50 Charlton Avenue East T3304, Hamilton, Ontario, Canada L8N 4A6.|Firestone Institute for Respiratory Health and Department of Medicine, McMaster University, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6.
authors.forename: Paul
authors.initials: P
authors.lastname: Forsythe
authors.affiliation: McMaster Brain-Body Institute at St Joseph's Healthcare Hamilton, 50 Charlton Avenue East T3304, Hamilton, Ontario, Canada L8N 4A6.|Department of Pathology and Molecular Medicine, McMaster University, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6.
authors.forename: John
authors.identifier: 0000-0002-7677-0867
authors.initials: J
authors.lastname: Bienenstock
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000502:physiology*; D007778:Lactobacillus / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D010404:Penicillin V / Q000008:administration & dosage* / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D019936:Probiotics / Q000008:administration & dosage; D012919:Social Behavior
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D010404:Penicillin V