title: Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Anastasia I
authors.initials: AI
authors.lastname: Petra
authors.affiliation: Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Smaro
authors.initials: S
authors.lastname: Panagiotidou
authors.affiliation: Second Department of Internal Medicine, Attikon General Hospital, Athens Medical School, Athens, Greece.
authors.forename: Erifili
authors.initials: E
authors.lastname: Hatziagelaki
authors.affiliation: Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Stewart
authors.affiliation: Department of Medical Sciences, Immunology Division, University of Chieti, Via dei Vestini, Chieti, Italy.
authors.forename: Pio
authors.initials: P
authors.lastname: Conti
authors.affiliation: Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, Massachusetts; Department of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts; Department of Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts. Electronic address: theoharis.theoharides@tufts.edu.
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D001007:Anxiety / Q000276:immunology / Q000382:microbiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000276:immunology / Q000382:microbiology; D001921:Brain / Q000503:physiopathology*; D016207:Cytokines / Q000276:immunology; D003863:Depression / Q000276:immunology / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D009103:Multiple Sclerosis / Q000276:immunology / Q000382:microbiology; D009422:Nervous System Diseases / Q000276:immunology / Q000382:microbiology*; D015213:Neuroimmunomodulation / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000503:physiopathology
chemical_list: D016207:Cytokines
keywords: MGB axis; cytokines; gut; immune disorders; microbiota; nervous system diseases