Neuroendocrine Signalling Pathways Along the Microbiota-Gut-Brain Axis in Functional Gut Disorders

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Background

Functional gastrointestinal disorders (FGIDs) are a group of gut disorders with increasing incidence worldwide, mainly represented by irritable bowel syndrome and functional dyspepsia, lacking organic pathophysiological basis and characterized by non-structural symptoms that destabilize the patient's quality of life. Although the exact etiopathogenesis remains unknown, FGDIs symptoms develop as a consequence of dysmotility, visceral hyperalgesia, autonomic nervous system dysfunctions, familiarity, psychosocial triggers, postinfectious events. FGID clinical manifestations derive from the interplay between altered gut physiology and psychological factors where the gut and the brain influence each other via bidirectional communication pathways along the “gut-brain axis”. The gut microbiota, by secreting several neuroactive molecules, hormones and metabolites, participates in this bidirectional cross-talk, playing a pivotal role in maintaining local, systemic, and brain homeostasis. Research in the field of the microbiota-gut-brain axis will eventually lead to target specific neuroendocrine signaling pathways, using probiotics, prebiotics, or antibiotics, to treat gastrointestinal and/or psychiatric disorder associated with FGIDs.

Supplementation with prebiotic, probiotic, and fecal transplantation, determines changes in gut microbiota composition and are increasingly recognized as interesting therapeutic approaches to relieve gastrointestinal and psychiatric symptoms associated with FGIDs. However, the therapeutic value and the clinical outcomes of these strategies remain, to date, controversial. This may be due, at least in part, to the heterogeneity of the underlying pathophysiological mechanisms. This special issue aims to highlight the more recent advances in the involvement of neuroendocrine signaling pathways along the microbiota-gut-brain axis, in the pathogenesis of FGIDs. From the seminal discovery, about 30 years ago, of noradrenaline and adrenaline as neuroendocrine molecules along the microbiota-gut-brain axis, several neuroactive molecules such as serotonin, kynurenine, and indoles, deriving from tryptophan metabolism, neurotransmitters, such as glutamate, GABA and acetylcholine, neuroactive short and medium-chain fatty acids, secondary bile acids, branch chain amino acids are produced by the gut microflora. These microbially-derived molecules and their signaling pathways may influence both the gut and the brain activity giving rise to a microbiota-mediated bottom-up control of the CNS both in health conditions and in disease states, including FGIDs.

This special issue will include more recent evidence and advances on the involvement of neuroendocrine signaling pathways involved in the microbiota-gut-brain axis, comprising catecholamines (adrenaline, noradrenaline, dopamine), serotonin, kynurenine, indole, GABA, glutamate, and microbial metabolites such as short and medium-chain fatty acids, secondary bile acids and branch chain amino acids in the pathogenesis and symptom development of FGIDs. The issue will encompass original research articles and review articles.

Keywords: Functional Gastrointestinal Disorders, Irritable Bowel Syndrome (IBS), Microbiota-Gut-Brain Axis, Stress, Visceral Pain

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