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Upstairs-Downstairs- The Gut Microbiome as a Key Regulator of Brain and Behaviour

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There is a growing appreciation of the relationship between gut microbiota, and the host in maintaining homeostasis in health and predisposing to disease. Bacterial colonisation of the gut plays a major role in postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Individually, these systems have been implicated in the neuropathology of many CNS disorders and collectively they form an important bidirectional pathway of communication between the microbiota and the brain in health and disease. Over the past 5 years substantial advances have been made in linking alterations in microbiota to brain development and even behaviour and the concept of a microbiota-gut brain axis has emerged. Animal models have been essential in moving forward this frontier research area. In order to assess such a role we use studies involving, germ free mice and early-life microbiota manipulations and finally probiotic administration in adulthood. We assess neurochemical, molecular and behavioural effects following these manipulations. Our data show that the gut microbiota is essential for normal stress, antidepressant and anxiety responses. Moreover, microbiota is essential for both social cognition and visceral pain. Finally, there are critical time-windows early in life when the effects of microbiota on brain and behaviour appear to be more potent. Manipulation of the microbiota in early life by cesarean delivery, antibiotics or stress leads to long-lasting effects on brain and behavior. Our data also demonstrates that these effects may be mediated via the vagus nerve, spinal cord, or neuroendocrine systems. Such data offer the enticing proposition that specific modulation of the enteric microbiota by dietary means may be a useful “psychobiotic”-based strategy for both stress-related and neurodevelopmental disorders ranging from depression to autism.

BIOGRAPHY John F. Cryan is Professor & Chair, Dept. of Anatomy & Neuroscience, University College Cork. He received a B.Sc. (Hons) and PhD from the National University of Ireland, Galway, Ireland. He was a visiting fellow at the Dept Psychiatry, University of Melbourne, Australia (1997-1998), which was followed by postdoctoral fellowships at the University of Pennsylvania, Philadelphia, USA and The Scripps Research Institute, La Jolla, California. He spent four years at the Novartis Institutes for BioMedical Research in Basel Switzerland, as a LabHead, Behavioural Pharmacology prior to joining UCC in 2005 where he was a Senior Lecturer in Pharmacology in the School of Pharmacy and in the Dept. Pharmacology & Therapeutics UCC . Currently he is also a Principal Investigator in the Alimentary Pharmabiotic Centre (http://www.ucc.ie/research/apc/content). Prof. Cryan’s current research interests include the neurobiological basis of stress-related disorders including depression, anxiety and drug dependence. Moreover, his group is also focused on understanding the interaction between brain, gut & microbiome and how it applies to stress and immune-related disorders, including irritable bowel syndrome and obesity and neurodevelopmental disorders such as autism.

Prof. Cryan has an H-Index of 57 (Google Scholar) having published over 250 peer-reviewed articles and book chapters. Prof. Cryan is a Senior Editor of Neuropharmacology and of Nutritional Neuroscience and an Editor of British Journal of Pharmacology. He is Advisory Editor of Psychopharmacology; on the Board of Reviewing Editors of Brain Research; an Associate Editor of Frontiers in Behavioural Neuroscience; an Associate Editor of Frontiers in Psychopharmacology and Frontiers in Gastrointestinal Pharmacology; an Editorial Board Member of Neurogastroenterology & Motility, Behavioural Pharmacology; Neuroscience and Biobehavioral Reviews, Genes, Brain & Behavior and International Journal of Neuropsychopharmacology. He has edited books on “Behavioural Neurogenetics” (Springer Press, 2012) on”Depression: From Psychopathology to Pharmacotherapy” (Karger Press, 2010) and “Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease” (Springer Press, 2014). Prof Cryan received the inaugural University College Cork Researcher of the Year Award in 2012. Cryan has also been honoured with the European College of Neuropsychopharmacology (ECNP) Fellowship Award, the Wyeth Psychopharmacology Award from British Association of Psychopharmacology and the Young Scientist Award from the European Behavioural Pharmacology Society. He has received commercialisation awards from UCC in 2012 and 2013. Further, in 2013 he received the University of Utrecht Award for Excellence in Pharmaceutical Research and delivered the Royal Academy of Medicine in Ireland Conway Review Lecture and the De Pazzi Lecture at University College Cork. He gave the Wingate Lecture at Barts & The London School of Medicine and Dentistry in 2014. Moreover in 2014, he was also named a Thomson Reuters Highly Cited Researcher and was included in ‘The World’s Most Influential Scientific Minds’ report. Prof Cryan was also a TEDMED Invited Speaker in 2014.

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