Format

Send to

Choose Destination
Bioessays. 2018 Sep;40(9):e1800027. doi: 10.1002/bies.201800027. Epub 2018 Jul 13.

The Microbiota-Inflammasome Hypothesis of Major Depression.

Inserra A1,2,3, Rogers GB4,5, Licinio J1,2,6, Wong ML1,2,6.

Author information

1
Mind and Brain Theme, South Australian Health and Medical Research Institute, Adelaide, 5001, SA, Australia.
2
Department of Psychiatry, College of Medicine and Public Health, Flinders University, Bedford Park, 5042, SA, Australia.
3
Centre for Neuroscience, Flinders University, Bedford Park, 5042, Australia.
4
Infection and Immunity Theme, South Australia Health and Medical Research Institute, North TerracAdelaide, 5001, SA, Australia.
5
SAHMRI Microbiome Research Laboratory, Flinders University College of Medicine and Public Health, Bedford Park, 5001, SA, Australia.
6
State University of New York Upstate Medical University, Syracuse, NY, 13210, USA.

Abstract

We propose the "microbiota-inflammasome" hypothesis of major depressive disorder (MDD, a mental illness affecting the way a person feels and thinks, characterized by long-lasting feelings of sadness). We hypothesize that pathological shifts in gut microbiota composition (dysbiosis) caused by stress and gut conditions result in the upregulation of pro-inflammatory pathways mediated by the Nod-like receptors family pyrin domain containing 3 (NLRP3) inflammasome (an intracellular platform involved in the activation of inflammatory processes). This upregulation exacerbates depressive symptomatology and further compounds gut dysbiosis. In this review we describe MDD/chronic stress-induced changes in: 1) NLRP3 inflammasome; 2) gut microbiota; and 3) metabolic pathways; and how inflammasome signaling may affect depressive-like behavior and gut microbiota composition. The implication is that novel therapeutic strategies could emerge for MDD and co-morbid conditions. A number of testable predictions surface from this microbiota-gut-inflammasome-brain hypothesis of MDD, using approaches that modulate gut microbiota composition via inflammasome modulation, fecal microbiota transplantation, psychobiotics supplementation, or dietary change.

KEYWORDS:

NLRP3; depression; dysbiosis; gut microbiota; inflammasome; probiotics

PMID:
30004130
DOI:
10.1002/bies.201800027
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center