GUTPSY: Harnessing the gut microbiome to improve the tolerability and efficacy of antipsychotics

Around one in three patients with psychosis do not respond to antipsychotic medications, while side effects limit their use in two-thirds of patients. Preclinical evidence shows that gut bacteria can degrade and sequester antipsychotics; these, in turn, can inhibit bacterial growth. Moreover, I have recently shown in humans that the microbiome may contribute to inter-individual variation in the response and tolerability to antipsychotics. In this fellowship, I will: 1) Identify microbiome signatures associated with the efficacy and tolerability of both licenced antipsychotic medications and novel candidate treatments for psychosis. I will achieve this by assessing participants who are already being recruited to clinical services for psychosis, and to clinical trials of novel compounds. 2) Investigate mechanisms, test causality, and dissect the host-microbiome interactions putatively underlying these associations, using genome-scale metabolic reconstructions, in vitro and gnotobiotic models. My overall aim is to develop methods that will support a more personalised approach to treatment in psychosis, with the selection of medications informed by each individual’s microbiome profile, such that they receive the treatment that is most likely to be effective and least likely to cause side effects.