title: Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat.
abstract: Gut microbiota colonization is a key event for host physiology that occurs early in life. Disruption of this process leads to altered brain development which ultimately manifests as changes in brain function and behaviour in adulthood. Studies using germ-free (GF) mice highlight the extreme impact on brain health that results from life without commensal microbes. However, the impact of microbiota disturbances occurring in adulthood is less studied. To this end, we depleted the gut microbiota of 10-week-old male SpragueDawley rats via chronic antibiotic treatment. Following this marked, sustained depletion of the gut bacteria, we investigated behavioural and molecular hallmarks of gut-brain communication. Our results reveal that depletion of the gut microbiota during adulthood results in deficits in spatial memory as tested by Morris water maze, decreased visceral sensitivity and a greater display of depressive-like behaviours in the forced swim test. In tandem with these clear behavioural alterations we found changes in altered CNS serotonin concentration along with changes in the mRNA levels of corticotrophin releasing hormone receptor 1 and glucocorticoid receptor. Additionally, we found changes in the expression of brain derived neurotrophic factor (BDNF), a hallmark of altered microbiota-gut-brain axis signalling. In summary, this model of antibiotic-induced depletion of the gut microbiota can be used for future studies interested in the impact of the gut microbiota on host health without the confounding developmental influence of early-life microbial alterations.
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Ireland.
authors.forename: A E
authors.initials: AE
authors.lastname: Hoban
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland.
authors.forename: R D
authors.initials: RD
authors.lastname: Moloney
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland.
authors.forename: A V
authors.initials: AV
authors.lastname: Golubeva
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland.
authors.forename: K A
authors.initials: KA
authors.lastname: McVey Neufeld
authors.affiliation: Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.
authors.forename: O
authors.initials: O
authors.lastname: O'Sullivan
authors.affiliation: Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Patterson
authors.affiliation: Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.
authors.forename: C
authors.initials: C
authors.lastname: Stanton
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Ireland.
authors.forename: T G
authors.initials: TG
authors.lastname: Dinan
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Ireland.
authors.forename: G
authors.initials: G
authors.lastname: Clarke
authors.affiliation: APC Microbiome Institute, University College Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Ireland. Electronic address: j.cryan@ucc.ie.
authors.forename: J F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001007:Anxiety / Q000382:microbiology; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002432:Cecum / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000378:metabolism / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000378:metabolism / Q000382:microbiology*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D059265:Visceral Pain / Q000378:metabolism / Q000382:microbiology* / Q000523:psychology; D000099052:CRF Receptor, Type 1
chemical_list: D000900:Anti-Bacterial Agents; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D012701:Serotonin; D000099052:CRF Receptor, Type 1; D003345:Corticosterone
keywords: antibiotics; brain monoamines; cognition; depressive-like behaviours; gut microbiota; visceral sensitivity