The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine, and immunological mechanisms. There is mounting data that gut microbiota is the source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in the control of emotions, cognition, and physical activity. Most GI diseases are associated with altered transmission within the GBA that are influenced by both genetic and environmental factors. Current treatment protocols for GI and non-GI disorders may positively or adversely affect the composition of intestinal microbiota with a diverse impact on therapeutic outcome(s). Alterations of gut microbiota have been associated with mood and depressive disorders. Moreover, mental health is frequently affected in GI and non-GI diseases. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example, next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Elucidating the role of stem cell–host microbiome cross talks in tissues in GBA disorders might lead to the development of next generation diagnostics and therapeutics. Psychobiotics are a new class of beneficial bacteria with documented efficacy for the treatment of GBA disorders. Novel therapies interfering with small molecules involved in adult stem cell trafficking are on the horizon.
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