The gut microbiota in depression
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University College Cork
The accruing data linking the gut microbiota to the development and function of the central nervous system has been proposed as a paradigm shift in neuroscience. Neuroimmune, neuroendocrine and neural communication pathways exist between host and microbe. 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. Dysfunctional neuro-immune and neuro-endocrine pathways are implicated in stress-related psychiatric disorders. To this end, we proposed that the gut microbiota, by modulating these pathways, plays an influential role in the pathophysiology of depression. We demonstrated that depression is associated with altered gut microbiota composition with decreased richness and diversity. Furthermore, we have shown that transferring the gut microbiota 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. Although we provide evidence that the gut microbiota is altered in depression and that this alteration could have a role in prominent features of depression, an interventional study based on targeting the gut microbiota in healthy males using Lactobacillus rhamnosus (JB-1) was not superior to placebo in modifying self-reported stress, HPA axis response to an acute stressor, inflammation, cognition or neurophysiological measures. Taken together, these findings have furthered our understanding of the pathophysiology of depression. By incorporating the gut microbiota into existing neurobiological models of depression a more comprehensive model has been developed. The successful translation of this work could lead to stratification based on gut microbiome composition and could deliver further diagnostic accuracy to improve patient phenotyping for treatment selection in future studies in psychiatric populations. Furthermore, our findings advance the possibility of targeting the gut microbiome in the treatment and prevention of stress related disorders and offer an important future strategy in psychiatry.
Brain-gut axis , Depression , Inflammation , Intestinal barrier , Tryptophan , Psychobiotic , Gut microbiota
Kelly, J. 2016. The gut microbiota in depression. PhD Thesis, University College Cork.