Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat. (17th December 2016)

• Record Type: Journal Article
• Authors: Hoban, A.E.; Moloney, R.D.; Golubeva, A.V.; McVey Neufeld, K.A.; O'Sullivan, O.; Patterson, E.; Stanton, C.; Dinan, T.G.; Clarke, G.; Cryan, J.F.
• Is Part Of: Neuroscience. Volume 339(2016)
• Page Start: 463
• Page End: 477
• Publication Date: 2016-12-17
• Subjects: 5-HIAA 5-hydroxyindoleacetic acid -- BDNF brain derived neurotrophic factor -- CRD colorectal distension -- EDTA ethylenediaminetetraacetic acid -- EPM elevated plus maze -- FST forced swim test -- GF germ-free -- HPA hypothalamic–pituitaryadrenal -- HPLC high-performance liquid chromatography -- HVA homovanillic acid -- MWM Morris water maze -- NOR novel object recognition -- OF open field -- PCoA principal coordinate analysis; gut microbiota -- antibiotics -- cognition -- visceral sensitivity -- brain monoamines -- depressive-like behaviours; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.10.003
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Chronic antibiotic treatment affects visceral pain and CNS monoamine levels. Distinct behavioural profile after microbiota depletion. No change in anxiety and HPA axis. 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, increased 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.