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Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Journal

CLINICAL THERAPEUTICS
Volume 37, Issue 5, Pages 984-995

Publisher

ELSEVIER
DOI: 10.1016/j.clinthera.2015.04.002

Keywords

cytokines; gut; immune disorders; MGB axis; microbiota; nervous system diseases

Funding

  1. National Institutes of Health [NS38326, AR47652]
  2. Autism Collaborative
  3. Autism Research Institute
  4. National Autism Association
  5. Safe Minds
  6. Johnson B. Johnson Foundation
  7. Michael and Margaret Johnson Family Foundation
  8. Nancy Lurie Marks Foundation
  9. Theta Biomedical Consulting and Development Co, Inc.

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Purpose: Gut microbiota regulate intestinal function and health. However, mounting evidence indicates that they can also influence the immune and nervous systems and vice versa. This article reviews the bidirectional relationship between the gut microbiota and the brain, termed the microbiota-gut-brain (MGB) axis, and discusses how it contributes to the pathogenesis of certain disorders that may involve brain inflammation. Methods: Articles were identified with a search of Medline (starting in 1980) by using the key words anxiety, attention-deficit hypersensitivity disorder (ADHD), autism, cytokines, depression, gut, hypothalamic-pituitary-adrenal (HPA) axis, inflammation, immune system, microbiota, nervous system, neurologic, neurotransmitters, neuroimmune conditions, psychiatric, and stress. Findings: Various afferent or efferent pathways are involved in the MGB axis. Antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and essential metabolites all convey information to the central nervous system about the intestinal state. Conversely, the hypothalamic pituitary adrenal axis, the central nervous system regulatory areas of satiety, and neuropeptides released from sensory nerve fibers affect the gut microbiota composition directly or through nutrient availability. Such interactions seem to influence the pathogenesis of a number of disorders in which inflammation is implicated, such as mood disorder, autism-spectrum disorders, attention-deficit hypersensitivity disorder, multiple sclerosis, and obesity. Implications: Recognition of the relationship between the MGB axis and the neuroimmune systems provides a novel approach for better understanding and management of these disorders. Appropriate preventive measures early in life or corrective measures such as use of psychobiotics, fecal microbiota transplantation, and flavonoids are discussed. (C) 2015 Elsevier HS Journals, Inc. All rights reserved.

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