The Microbiota‐Inflammasome Hypothesis of Major Depression

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.

Remitted affective disorders and high familial risk of affective disorders associate with aberrant intestinal microbiota

“…Recent reports on the intestinal microbiota of human psychiatric disorders including depression and bipolar disorder report a similar pattern of reduced diversity. Other studies have also shown unaltered and also increased microbiome diversity in patients with depression as described in a recent paper introducing the microbiota‐inflammasome hypothesis . Based on results from seven studies on major depression, it was concluded that depression seems associated with altered microbiota composition .…”

“…Other studies have also shown unaltered and also increased microbiome diversity in patients with depression as described in a recent paper introducing the microbiota‐inflammasome hypothesis . Based on results from seven studies on major depression, it was concluded that depression seems associated with altered microbiota composition . The altered microbiota diversity in the referred psychiatric disorders may be related to intrinsic disease heritability per se as well as to adjunct lifestyle factors including diet, smoking, and alcohol consumption as well as medication use.…”

The changes of gut microbiota in drug-naïve first-episode MDD patients under treatment by SSRIs

“…As a common mental disorder accompanied by high disability and suicide, major depressive disorder MDD has become a worldwide issue concerned [1]. In recent years, more and more evidences were reported to indicate that gut microbes might take part in the course of MDD [2][3][4]. In several paralleled researches, MDD patients showed speci c features of gut microbes differing from normal controls [5][6][7][8].…”

Mitochondria could be a potential key mediator linking the intestinal microbiota to depression

“…[10][11][12] For example, it has been shown that the Bacteroides genus in patients with MDD was increased, while the Lachnospiraceae genus was decreased. 5,14,15 Further consideration on the mechanisms central to the role that gut microorganisms may have on the pathogenesis of MDD is of significant importance. Emerging evidence with the administration of probiotics has demonstrated a decrease in neuroinflammation, a pathogenic characteristic of depression.…”

“…Emerging evidence with the administration of probiotics has demonstrated a decrease in neuroinflammation, a pathogenic characteristic of depression. 5,14,15 Further consideration on the mechanisms central to the role that gut microorganisms may have on the pathogenesis of MDD is of significant importance.…”