Cited by 592Gut microbiota and healthTryptophan and brain disordersGastrointestinal motility and disorders

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

Open access
Petra, Anastasia I., Panagiotidou, Smaro, Hatziagelaki, Erifili, Stewart, Julia M., Conti, Pio, Theoharides, Theoharis C.·2015·Clinical Therapeutics

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.clinthera.2015.04.002

Cites

146 of 146 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Gastrointestinal microbiota could play a pivotal role in the etiology of psychiatric illness and make individuals more susceptible to develop psychopathology after ELS/CT.

    “which could play a pivotal role in the etiology of psychiatric illness and make individuals more susceptible to develop psychopathology after ELS/CT (241, 248, 249).”

    From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [248]

    The Abstract (Findings; page unavailable) says gut–brain interactions appear to influence the pathogenesis of mood and other neuropsychiatric disorders. The Introduction (page unavailable) reports that maternal-separation stress changes gut microbiota, but it does not say that microbiota makes people more susceptible to psychopathology after early-life stress or childhood trauma. (LLM, conf=0.85)

    Experimental — accuracy not yet measured
  • Dietary intake and the microbiome are potent modulators of inflammatory pathways.

    “Finally, it is important to note that dietary intake and the microbiome are potent modulators of inflammatory pathways (Kiecolt-Glaser, 2010;Petra et al, 2015)”

    From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Petra et al, 2015

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. [22]Theoharidess TC Irritable Bowel Syndrome and Ulcerative Colitis: Mast Cell Numbers are Increased, but Activation is more important Dig Dis Sc 2014 59 5 897 898 24445729 PMC7003572
  2. [97]Berer K Mues M Koutrolos M Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination Nature 2011 479 7374 538 541 22031325

Cited by

Sorted by citations

Authors
Petra, A. I., Panagiotidou, S., Hatziagelaki, E., Stewart, J. M., Conti, P., & Theoharides, T. C.
Affiliations
  • Tufts University (US)
  • University General Hospital Attikon (GR)
  • University of Chieti-Pescara (IT)
Corresponding author
Theoharides, Theoharis C.
Venue
Clinical Therapeutics
Publisher
Elsevier BV
Published
2015-05
Volume
37
Issue
5
Pages
984-995
ISSN
0149-2918 (ISSN-L)
OpenAlex
W1603039868
Cited by
592
References
146
Citations by year
2026: 22 · 2025: 54 · 2024: 47 · 2023: 53 · 2022: 76 · 2021: 72 · 2020: 70 · 2019: 56 · 2018: 52 · 2017: 52 · 2016: 31 · 2015: 7
FWCI
4.59
Type
journal article
Language
en
Open access
Locations
  • Clinical Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Johnson Family Foundation
  • Autism Research Institute
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (NS38326, R01NS038326)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 47652, R01AR047652)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
gut microbiota, microbiota-gut-brain axis, neuroinflammation, immune dysregulation, anxiety, depression, attention deficit hyperactivity disorder, autism spectrum disorder, multiple sclerosis, obesity, hypothalamic-pituitary-adrenal axis, cytokines, vagal afferent pathways, psychobiotics, fecal microbiota transplantation, flavonoids, neuropsychiatric disorders
MeSH terms
Gastrointestinal Microbiome, Anxiety, Attention Deficit Disorder with Hyperactivity, Brain, Depression, Humans, Hypothalamo-Hypophyseal System, Multiple Sclerosis, Nervous System Diseases, Pituitary-Adrenal System, Neuroimmunomodulation, Cytokines

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review