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dc.contributor.author
Lynch, Caoimhe M.K.
dc.contributor.author
Cowan, Caitlin S.M.
dc.contributor.author
Bastiaanssen, Thomaz F.S.
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Moloney, Gerard M.
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Theune, Nigel
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van de Wouw, Marcel
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Florensa Zanuy, Eva
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Ventura Silva, Ana Paula
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Codagnone, Martín Gabriel
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Villalobos Manríquez, Francisca
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Segalla, Matilde
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Koc, Fatma
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Stanton, Catherine
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Ross, Paul
dc.contributor.author
Dinan, Timothy G.
dc.contributor.author
Clarke, Gerard
dc.contributor.author
Cryan, John F.
dc.date.available
2024-02-21T14:02:48Z
dc.date.issued
2023-02
dc.identifier.citation
Lynch, Caoimhe M.K.; Cowan, Caitlin S.M.; Bastiaanssen, Thomaz F.S.; Moloney, Gerard M.; Theune, Nigel; et al.; Critical windows of early-life microbiota disruption on behaviour, neuroimmune function, and neurodevelopment; Academic Press Inc Elsevier Science; Brain Behavior And Immunity; 108; 2-2023; 309-327
dc.identifier.issn
0889-1591
dc.identifier.uri
http://hdl.handle.net/11336/227791
dc.description.abstract
Numerous studies have emphasised the importance of the gut microbiota during early life and its role in modulating neurodevelopment and behaviour. Epidemiological studies have shown that early-life antibiotic exposure can increase an individual's risk of developing immune and metabolic diseases. Moreover, preclinical studies have shown that long-term antibiotic-induced microbial disruption in early life can have enduring effects on physiology, brain function and behaviour. However, these studies have not investigated the impact of targeted antibiotic-induced microbiota depletion during critical developmental windows and how this may be related to neurodevelopmental outcomes. Here, we addressed this gap by administering a broad-spectrum oral antibiotic cocktail (ampicillin, gentamicin, vancomycin, and imipenem) to mice during one of three putative critical windows: the postnatal (PN; P2-9), pre-weaning (PreWean; P12-18), or post-weaning (Wean; P21-27) developmental periods and assessed the effects on physiology and behaviour in later life. Our results demonstrate that targeted microbiota disruption during early life has enduring effects into adolescence on the structure and function of the caecal microbiome, especially for antibiotic exposure during the weaning period. Further, we show that microbial disruption in early life selectively alters circulating immune cells and modifies neurophysiology in adolescence, including altered myelin-related gene expression in the prefrontal cortex and altered microglial morphology in the basolateral amygdala. We also observed sex and time-dependent effects of microbiota depletion on anxiety-related behavioural outcomes in adolescence and adulthood. Antibiotic-induced microbial disruption had limited and subtle effects on social behaviour and did not have any significant effects on depressive-like behaviour, short-term working, or recognition memory. Overall, this study highlights the importance of the gut microbiota during critical windows of development and the subtle but long-term effects that microbiota-targeted perturbations can have on brain physiology and behaviour.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Academic Press Inc Elsevier Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
ADOLESCENCE
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ADULTHOOD
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BEHAVIOUR
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CRITICAL WINDOWS
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DEVELOPMENT
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EARLY LIFE
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GUT MICROBIOTA
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IMMUNE
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MICROGLIA
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MYELIN
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Neurociencias
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Critical windows of early-life microbiota disruption on behaviour, neuroimmune function, and neurodevelopment
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-02-20T13:21:53Z
dc.journal.volume
108
dc.journal.pagination
309-327
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Lynch, Caoimhe M.K.. University College Cork; Irlanda
dc.description.fil
Fil: Cowan, Caitlin S.M.. University College Cork; Irlanda
dc.description.fil
Fil: Bastiaanssen, Thomaz F.S.. University College Cork; Irlanda
dc.description.fil
Fil: Moloney, Gerard M.. University College Cork; Irlanda
dc.description.fil
Fil: Theune, Nigel. University College Cork; Irlanda
dc.description.fil
Fil: van de Wouw, Marcel. University College Cork; Irlanda
dc.description.fil
Fil: Florensa Zanuy, Eva. University College Cork; Irlanda
dc.description.fil
Fil: Ventura Silva, Ana Paula. University College Cork; Irlanda
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Fil: Codagnone, Martín Gabriel. University College Cork; Irlanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
dc.description.fil
Fil: Villalobos Manríquez, Francisca. University College Cork; Irlanda
dc.description.fil
Fil: Segalla, Matilde. University College Cork; Irlanda
dc.description.fil
Fil: Koc, Fatma. Moorepark Food Research Centre; Irlanda. University College Cork; Irlanda
dc.description.fil
Fil: Stanton, Catherine. University College Cork; Irlanda. Moorepark Food Research Centre; Irlanda
dc.description.fil
Fil: Ross, Paul. University College Cork; Irlanda. Moorepark Food Research Centre; Irlanda
dc.description.fil
Fil: Dinan, Timothy G.. University College Cork; Irlanda
dc.description.fil
Fil: Clarke, Gerard. University College Cork; Irlanda
dc.description.fil
Fil: Cryan, John F.. University College Cork; Irlanda
dc.journal.title
Brain Behavior And Immunity
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bbi.2022.12.008
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0889159122004664
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