The HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota?
Author: Misiak B1, Łoniewski I2, Marlicz W3, Frydecka D4, Szulc A5, Rudzki L6, Samochowiec J7
Affiliation:
1Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1 Street, 50-368 Wroclaw, Poland. Electronic address: blazej.misiak@umed.wroc.pl.
2Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland.
3Department of Gastroenterology, Pomeranian Medical University, Unii Lubelskiej 1 Street, 71-252 Szczecin, Poland.
4Department of Psychiatry, Wroclaw Medical University, Pasteura 10 Street, 50-367 Wroclaw, Poland.
5Department of Psychiatry, Medical University of Warsaw, Poland.
6The Charleston Centre, 49 Neilston Road, Paisley PA2 6LY, United Kingdom.
7Department of Psychiatry, Pomeranian Medical University, Broniewskiego 26 Street, 71-460 Szczecin, Poland.
Conference/Journal: Prog Neuropsychopharmacol Biol Psychiatry.
Date published: 2020 Apr 23
Other:
Volume ID: 109951 , Special Notes: doi: 10.1016/j.pnpbp.2020.109951. [Epub ahead of print] , Word Count: 266
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.
Copyright © 2019. Published by Elsevier Inc.
KEYWORDS: Cortisol; Glucocorticoid; Intestine; Microbe; Microbiome
PMID: 32335265 DOI: 10.1016/j.pnpbp.2020.109951
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