Transferring the blues: Depression-associated gut microbiota inducesneurobehavioural changes in the rat

John R Kelly, Yuliya Borre, Ciaran O' Brien, Elaine Patterson, Sahar El Aidy, Jennifer Deane, Paul Kennedy, Sasja Beers, Karen Scott, Gerard Maloney, Alan E Hoban, Lucinda Scott, Patrick Fitzgerald, Ross Paul, Catherine Stanton, Gerald Clarke, John F Cryan, Timothy G Dinan

    Research output: Contribution to journalArticle

    204 Citations (Scopus)

    Abstract

    The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways.These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gut microbiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.
    LanguageEnglish
    Pages109-118
    JournalJournal of Psychiatric Research
    Volume82
    Early online date25 Jul 2016
    DOIs
    Publication statusE-pub ahead of print - 25 Jul 2016

    Fingerprint

    Depression
    Microbiota
    Tryptophan
    Anhedonia
    Kynurenine
    Neural Pathways
    Brain
    Hydrocortisone
    Anxiety
    Enzyme-Linked Immunosorbent Assay
    High Pressure Liquid Chromatography
    Gastrointestinal Microbiome
    Cytokines
    Fecal Microbiota Transplantation
    Therapeutics

    Keywords

    • Gut Microbiota
    • depression
    • neuroscience

    Cite this

    Kelly, J. R., Borre, Y., O' Brien, C., Patterson, E., El Aidy, S., Deane, J., ... Dinan, T. G. (2016). Transferring the blues: Depression-associated gut microbiota inducesneurobehavioural changes in the rat. 82, 109-118. https://doi.org/10.1016/j.jpsychires.2016.07.019
    Kelly, John R ; Borre, Yuliya ; O' Brien, Ciaran ; Patterson, Elaine ; El Aidy, Sahar ; Deane, Jennifer ; Kennedy, Paul ; Beers, Sasja ; Scott, Karen ; Maloney, Gerard ; Hoban, Alan E ; Scott, Lucinda ; Fitzgerald, Patrick ; Paul, Ross ; Stanton, Catherine ; Clarke, Gerald ; Cryan, John F ; Dinan, Timothy G. / Transferring the blues: Depression-associated gut microbiota inducesneurobehavioural changes in the rat. 2016 ; Vol. 82. pp. 109-118.
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    abstract = "The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways.These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gut microbiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.",
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    Kelly, JR, Borre, Y, O' Brien, C, Patterson, E, El Aidy, S, Deane, J, Kennedy, P, Beers, S, Scott, K, Maloney, G, Hoban, AE, Scott, L, Fitzgerald, P, Paul, R, Stanton, C, Clarke, G, Cryan, JF & Dinan, TG 2016, 'Transferring the blues: Depression-associated gut microbiota inducesneurobehavioural changes in the rat', vol. 82, pp. 109-118. https://doi.org/10.1016/j.jpsychires.2016.07.019

    Transferring the blues: Depression-associated gut microbiota inducesneurobehavioural changes in the rat. / Kelly, John R; Borre, Yuliya; O' Brien, Ciaran; Patterson, Elaine; El Aidy, Sahar; Deane, Jennifer; Kennedy, Paul; Beers, Sasja; Scott, Karen; Maloney, Gerard; Hoban, Alan E; Scott, Lucinda; Fitzgerald, Patrick; Paul, Ross; Stanton, Catherine; Clarke, Gerald; Cryan, John F; Dinan, Timothy G.

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    Research output: Contribution to journalArticle

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    AU - Deane, Jennifer

    AU - Kennedy, Paul

    AU - Beers, Sasja

    AU - Scott, Karen

    AU - Maloney, Gerard

    AU - Hoban, Alan E

    AU - Scott, Lucinda

    AU - Fitzgerald, Patrick

    AU - Paul, Ross

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    AU - Clarke, Gerald

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