Developing a Pathway to Personalised Medicine in Psychiatry
Hyland, Niall, Senior Lecturer (Associate Professor)
University College Cork - National University of Ireland
The microbiome plays a key role in health and disease and there has been considerable interest in therapeutic targeting of the microbiome as well as mining this rich resource in drug discovery efforts. However, a growing body of evidence now suggests that the gut microbiota can itself influence the actions of a range of drugs both by directly metabolising them and indirectly by affecting host drug metabolism, the consequences of which can be either beneficial or potentially harmful. Nevertheless, such studies have not extended to psychotropic medications nor addressed whether the dysbiosis associated with psychiatric illness may underpin the clinical response to psychotropic drugs.
The objectives of the project are to determine the impact of clinically diagnosed depression on microbial drug metabolism; to identify whether depression-associated dysbiosis affects host drug metabolism and drug pharmacokinetics in a humanised rat model of depression; and to develop a Physiologically based Pharmacokinetic (PbPK) model incorporating a microbiome-mediated drug metabolism compartment for predicting drug pharmacokinetics in patients.
The project will measure the drug-metabolising activity of the gut microbiome from patients with depression by preparing a stable cell-free extract of human faeces, fecalase. Using high performance liquid chromatography the researchers will then determine whether fecalase from depressed subjects differentially affects the metabolism of psychotropic drugs. To better understand the impact of disease-driven dysbiosis on host drug metabolism and pharmacokinetics, in a humanised rat model of depression they will examine the expression of genes involved in host drug metabolism and the pharmacokinetic profile of psychotropic medications. Finally, through the incorporation of different types of data, including -omics, enzymatic and pharmacokinetic data in an integrated way they will develop an in silico model which can be tailored to the individual patient characteristics and provide reliable predictions of drug levels in these patients.
Dr Hyland is a tenured Senior Lecturer in the Department of Physiology and Faculty in APC Microbiome Ireland at University College Cork, Ireland. He received a BSc (Hons) in Biomedical Sciences from the University of Ulster and PhD in Pharmacology from King’s College London. Niall was a visiting fellow at the Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center (1998-1999) and completed an AstraZeneca/Canadian Association of Gastroenterology/Canadian Institutes of Health Research-funded postdoctoral fellowship at the University of Calgary in Canada. He returned to Ireland in 2007 to take up a GlaxoSmithKline-supported senior postdoctoral position at APC Microbiome Ireland and was subsequently appointed Lecturer in Pharmacology in the School of Medicine in 2008 and Senior Lecturer in Physiology in 2018.
Niall’s laboratory investigates the interactions between the gut microbiome and host in the context of intestinal physiology and the gut-brain axis. Current collaborative projects are investigating microbial drug metabolism; the bladder microbiome;
and the temporal changes in the gut microbiome during colon carcinogenesis. Dr Hyland has a H-Index of 22 and co-edited
the book, The Gut-Brain Axis: Dietary, Probiotic, and Prebiotic Interventions on the Microbiota published by Elsevier/Academic Press.