Gut Microbiome alterations in Depression: relevance to pathophysiology
Kelly JR1,2, Borre Y1, O’ Brien C3, El Aidy S1,4, Deane J3, Patterson E3, Kennedy1 PJ, Beers S1, Scott K1, Moloney G1, Scott L2, Ross P3, Stanton C3, Cryan JF1,5, Dinan TG1,2, Clarke G1,2
1APC Microbiome Institute, University College Cork, Cork, Ireland. 2Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland. 3Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland. 4Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands. 5Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
Pre-clinical evidence suggests that the microbiota can recruit the brain-gut communication system to modulate brain development, function and behaviour.
The pathophysiology of depression involves neuroimmune-endocrine dysregulation, however, the extent to which changes in the gut microbiota composition and function mediate dysregulation of these pathways in depression is currently 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 16sRNA metagenomic sequencing. A FMT was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient antibiotic rat model.
Depression is associated with altered gut microbiota composition, richness and phylogenetic diversity. We show that FMT from depressed patients to microbiota-deficient rats can induce the development of behavioural and physiological features of depression in the recipient animals. This includes anhedonia and anxiety like behaviours, altered tryptophan metabolism and a decrease in intestinal transit time.
Our results confirm that depression is associated with a distinct microbial signature which is capable of inducing alterations in behaviour, neurobiology and gastrointestinal physiology when transferred to microbiota-deficient animals. This suggests that the gut microbiota may play a causal role in the development of core behavioural and neurobiological features of depression and may provide a tractable target in the treatment and prevention of depression.