Investigating the Physiological Effects of Gut Therapeutics in a Psychiatric Popualtion

Abstract

Background: There is a growing body of literature investigating the psychiatric applications of gut microbiome therapeutics. A comprehensive characterisation of this field and novel analyses of physiological changes associated with microbiome manipulation in psychiatry is helpful for identifying the consensuses and limitations of the field. Objectives: 1) Characterise the current landscape of the field of gut microbiome manipulation in psychiatry; 2) Characterise the current understanding of the mechanisms of action for gut microbiome therapeutics, and their physiological effects in the context of psychiatry; 3) Investigate the neurophysiological and microbial effects of probiotics in a psychiatric population. Methods: To accomplish the aforementioned objectives, numerous narrative and systemic reviews were conducted to evaluate the clinical, physiological, and neurobiological effects of probiotics and fecal microbiota transplantation in psychiatry. Microbial and functional neuroimaging data from the CAN-BIND 12: Effects of Probiotics on Symptoms of Depression clinical trial was then analysed, marking the first analysis of resting state functional connectivity changes associated with probiotic monotherapy to be conducted in individuals with major depressive disorder. Results: The findings from the reviews suggest probiotics may be effective in treating depressive disorders and could have some anxiolytic properties but may be most effective when administered as an adjuvant treatment. Fecal microbiota transplantation may have a greater immediate effect on psychiatric symptoms, but these effects may be transient in nature. Probiotic intervention has been associated with certain neurobiological changes, and these changes could play a role in ameliorating psychiatric symptoms, but the analysis in chapter 5 found the probiotic intervention to not be associated with resting state functional connectivity changes traditionally associated with antidepressant response or depression symptom improvement, and to not have generally beneficial effect on the alpha diversity of the gut microbiota. Conclusions: While there is a consensus in the field on the potential to effect psychiatric symptoms through manipulation of the gut microbiome, the evidence is mixed regarding the clinical effectiveness of gut microbiome therapeutics for treating psychiatric illnesses, and the findings form the primary analysis in chapter 5 suggests they may not affect positive change through altering resting state functional connectivity.