Cited by 343Gut microbiota and healthStress Responses and CortisolGastrointestinal motility and disorders

The HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota?

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Misiak, Błażej, Łoniewski, Igor, Marlicz, Wojciech, Frydecka, Dorota, Szulc, Agata, Rudzki, Leszek, Samochowiec, Jerzy·2020·Progress in Neuro-Psychopharmacology and Biological Psychiatry

Abstract

Accumulating evidence indicates that patients with severe mental disorders, including major depression, bipolar disorder and schizophrenia present with various alterations of the gut microbiota and increased intestinal permeability. In addition, the hypothalamic-pituitary-adrenal (HPA) axis dysregulation and subclinical inflammation have been reported in this group of patients. Although it has been found that the HPA axis dysregulation appears as a consequence of psychosocial stress, especially traumatic life events, the exact mechanisms of this observation remain unclear. Animal model studies have unraveled several mechanisms linking the gut microbiota with the HPA axis dysfunction. Indeed, the gut microbiota can activate the HPA axis through several mediators that cross the blood-brain barrier and include microbial antigens, cytokines and prostaglandins. There is also evidence that various microbial species can affect ileal corticosterone production that may impact the activity of the HPA axis. However, some metabolites released by various microbes, e.g., short-chain fatty acids, can attenuate the HPA axis response. Moreover, several bacteria release neurotransmitters that can directly interact with vagal afferents. It has been postulated that the HPA axis activation can impact the gut microbiota and intestinal permeability. In this article, we discuss various mechanisms linking the gut microbiota with the HPA axis activity and summarize current evidence for a cross-talk between the gut-brain axis and the HPA axis from studies of patients with mood and psychotic disorders. Finally, we show potential clinical implications that can arise from future studies investigating the HPA axis activity with respect to the gut microbiota in severe mental disorders.

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  • Chronic systemic inflammation linked to leaky gut syndrome disrupts the hypothalamus-pituitary-adrenal axis, resulting in increased production of glucocorticoids and catecholamines, causing hypercortisolemia and HPA axis overactivation, often accompanied by impaired glucocorticoid receptor function.

    “Chronic systemic inflammation linked to LGS also disrupts the hypothalamus–pituitary–adrenal (HPA) axis, a key system for providing high-energy fuels such as glucose, amino acids, and free fatty acids to support immune activity. This disruption results in the increased production of glucocorticoids and catecholamines, causing hypercortisolemia and HPA axis overactivation, often accompanied by”
  • Dysbiosis leads to heightened stress responses with elevated cortisol and ACTH levels.

    “Dysbiosis leads to heightened stress responses with elevated cortisol and adrenocorticotropic hormone (ACTH) levels [141,142].”
  • HPA axis dysfunction is associated with many major psychopathologies, including autism, anxiety disorders, depression, and schizophrenia, as well as other cognitive disorders.

    “HPA axis dysfunction is also associated with many major psychopathologies, including autism, anxiety disorders, depression, and schizophrenia, as well as other cognitive disorders (145).”

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Authors
Misiak, B., Łoniewski, I., Marlicz, W., Frydecka, D., Szulc, A., Rudzki, L., & Samochowiec, J.
Affiliations
  • Wroclaw Medical University (PL)
  • Pomeranian Medical University (PL)
  • Medical University of Warsaw (PL)
Corresponding author
Misiak, Błażej
Venue
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Publisher
Elsevier BV
Published
2020-08
Volume
102
Pages
109951
ISSN
0278-5846 (ISSN-L)
OpenAlex
W3018120946
Cited by
343
References
147
Citations by year
2026: 47 · 2025: 73 · 2024: 77 · 2023: 64 · 2022: 47 · 2021: 26 · 2020: 9
FWCI
3.49
Type
journal article
Language
en
Open access
Locations
  • Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Narodowe Centrum Nauki
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
HPA axis dysregulation, gut microbiota, gut-brain axis, severe mental illness, major depressive disorder, bipolar disorder, schizophrenia, intestinal permeability, subclinical inflammation, psychosocial stress, traumatic life events, short-chain fatty acids, vagal afferents, blood-brain barrier, corticosterone, microbial metabolites
MeSH terms
Gastrointestinal Microbiome, Mental Disorders, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System

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