From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

Ghrelin plays a role in various physiological and pathophysiological brain functions

The ghrelin receptor is now known to play an important role in regulating physiological responses to stress. In particular, ghrelin acting at the growth hormone secretagogue receptor (ghrelin receptor) may promote anxious behaviours under non-stressed conditions, and attenuate anxiety under conditions of stress. Dysregulation of the ghrelin system therefore has significant consequences for stress-related mood disorders such as anxiety and depression; disorders that pose a substantial problem for human health. These effects of the ghrelin system on mood are of particular concern in obese populations, where the likelihood of a mood disorder is higher and the ghrelin system disrupted. Studies in humans are still revealing conflicting roles for ghrelin and the ghrelin receptor in anxiety and depression, but these, and studies in animal models, offer evidence that ghrelin may influence its receptor at extra-hypothalamic brain regions to exert indirect control over central responses to stress and over brain pathways related to anxiety and depression. In this chapter, I discuss the background and potential mechanisms for ghrelin and ghrelin receptor's role in regulating stress and stress-related mood disorders