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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.

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


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.


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

[Indexed for MEDLINE]

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