Lieve Desbonnet1, Gerard Clarke2, Alexander Traplin3, Orla O'Sullivan4, Fiona Crispie4, Rachel D Moloney5, Paul D Cotter6, Timothy G Dinan2, John F Cryan7. 1. Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Electronic address: Lieve.Desbonnet@glasgow.ac.uk. 2. Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Psychiatry, University College Cork, Cork, Ireland. 3. School of Medicine, University College Cork, Cork, Ireland. 4. Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland. 5. Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. 6. Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland. 7. Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
Abstract
BACKGROUND: There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. METHODS: Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. RESULTS: Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. CONCLUSIONS: Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may contribute to the pathogenesis of disorders associated with altered anxiety and cognition.
BACKGROUND: There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. METHODS:Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. RESULTS: Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. CONCLUSIONS: Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may contribute to the pathogenesis of disorders associated with altered anxiety and cognition.
Authors: Christopher T Fields; Timothy R Sampson; Annadora J Bruce-Keller; Drew D Kiraly; Elaine Y Hsiao; Geert J de Vries Journal: J Neurosci Date: 2018-10-31 Impact factor: 6.167
Authors: Kirsten Tillisch; Emeran A Mayer; Arpana Gupta; Zafar Gill; Rémi Brazeilles; Boris Le Nevé; Johan E T van Hylckama Vlieg; Denis Guyonnet; Muriel Derrien; Jennifer S Labus Journal: Psychosom Med Date: 2017-10 Impact factor: 4.312