The microbiota-gut-brain axis in social anxiety disorder

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Butler, Mary I.
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University College Cork
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The past decade has seen huge interest in the role of microbiota-gut-brain (MGB) axis in psychiatric disorders. Significant preclinical efforts have been made to elucidate the role of the gut microbiome in the stress response, and there is an ever-growing body of evidence demonstrating the effect of gut microbiome modulation on behaviour in various animal models of anxiety and depression. Additionally, studies in healthy human volunteers have generated hope that microbiome-based interventions may improve mood and anxiety symptoms. Despite this, the MGB axis remains largely unexplored in patients with clinical anxiety disorders, such as social anxiety disorder (SAD). Indeed, investigation of the neurobiological basis of this and other clinical anxiety conditions is limited, and these disorders remain poorly understood. To this end, we hypothesized that the gut microbiota would be altered in those with SAD, and that gut barrier dysfunction would be evident. We proposed that physiological systems of relevance in MGB communication, including neuroendocrine, immune, and tryptophan-kynurenine pathways would show differences compared to controls. In this thesis, we demonstrate that the gut microbiome is compositionally and functionally altered in patients with SAD, and that this patient group have compromised intestinal permeability. We demonstrate that SAD is associated with differences in various systems involved in MGB communication. We report elevated kynurenic acid (KYNA) levels and an increased KYNA/Kynurenine ratio in our patient group. Additionally, SAD patients show lower levels of the anti-inflammatory cytokine, interleukin-10, along with various neuroendocrine alterations including lower oxytocin levels and differences in the cortisol awakening response, chronic cortisol concentrations and morning salivary alpha amylase levels. Taken together, our results raise the possibility that the MGB axis may represent an important aetiological node and potential therapeutic target for this early-onset, chronic disorder. Our work supports the need for larger, longitudinal studies to further explore the role of the MGB axis in clinical anxiety disorders. In addition, we report on a longitudinal study assessing the impact of a dietary change involving the consumption of unpasteurised dairy, on the gut microbiome of healthy volunteers. We demonstrate that intake of unpasteurised dairy is associated with significant increases in Lactobacillus, a psychobiotic bacterial genus which is recognised as having anxiolytic and antidepressant effects. This work supports the possibility that dietary change may have therapeutic potential in psychiatric conditions.
Microbiota-gut-brain axis , Gut microbiome , Social anxiety disorder
Butler, M. I. 2021. The microbiota-gut-brain axis in social anxiety disorder. PhD Thesis, University College Cork.