The Gut Microbiota Links Dietary Polyphenols With Management of Psychiatric Mood Disorders - PubMed (original) (raw)

Review

Susan Westfall et al. Front Neurosci. 2019.

Abstract

The pathophysiology of depression is multifactorial yet generally aggravated by stress and its associated physiological consequences. To effectively treat these diverse risk factors, a broad acting strategy is required and is has been suggested that gut-brain-axis signaling may play a pinnacle role in promoting resilience to several of these stress-induced changes including pathogenic load, inflammation, HPA-axis activation, oxidative stress and neurotransmitter imbalances. The gut microbiota also manages the bioaccessibility of phenolic metabolites from dietary polyphenols whose multiple beneficial properties have known therapeutic efficacy against depression. Although several potential therapeutic mechanisms of dietary polyphenols toward establishing cognitive resilience to neuropsychiatric disorders have been established, only a handful of studies have systematically identified how the interaction of the gut microbiota with dietary polyphenols can synergistically alleviate the biological signatures of depression. The current review investigates several of these potential mechanisms and how synbiotics, that combine probiotics with dietary polyphenols, may provide a novel therapeutic strategy for depression. In particular, synbiotics have the potential to alleviate neuroinflammation by modulating microglial and inflammasome activation, reduce oxidative stress and balance serotonin metabolism therefore simultaneously targeting several of the major pathological risk factors of depression. Overall, synbiotics may act as a novel therapeutic paradigm for neuropsychiatric disorders and further understanding the fundamental mechanisms of gut-brain-axis signaling will allow full utilization of the gut microbiota's as a therapeutic tool.

Keywords: gut-brain-axis; neuroinflammation; polyphenols; probiotics; resilience; synbiotics.

Copyright © 2019 Westfall and Pasinetti.

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Figures

FIGURE 1

FIGURE 1

Bioavailability of dietary polyphenols is primarily determined by the composition of the gut microbiota. As consumed, only 5% of dietary polyphenols are absorbed where consequently, Phase I and Phase II biotransformation takes place in the epithelial cells and liver which generates a limited battery of bioavailable metabolites. Upon reaching the lower colon, the gut microbiota breaks down the remaining dietary polyphenols through their endogenous enzymatic activity increasing their relative bioavailability for downstream processing by Phase I and Phase II biotransformation.

FIGURE 2

FIGURE 2

Gut microbiota activated inflammasome signaling leads to phenotypes specific to depression. Sterile inflammatory responses involving inflammasome signaling is a key mechanism of stress-induced depression and the gut microbiota has been shown to impact inflammasome signaling at several levels. Symbionts, or beneficial bacteria, have been shown to promote gut barrier integrity, and guide T-cell regulation toward an anti-inflammatory phenotype (green). Pathobionts, or bacteria with a negative effect, have the opposite effect, compromising the gut barrier integrity, activating immune response through the release of pathogen associated molecular patterns (PAMPs) and pushing T cell development toward a proinflammatory state (red). Overall, these effects lead to inflammasome activation in the periphery and the microglia that ultimately promote the development of depression.

FIGURE 3

FIGURE 3

Mechanisms connecting gastrointestinal dysbiosis with biological signature of depression. Depression is a multifaceted disorder with several coordinating pathologies, most which can be modulated by gut microbiota modifying agents including dietary polyphenols. The main gut-brain-axis mechanisms through which polyphenols and their microbial-derived metabolites can elicit a positive effect on depression are stress (yellow), serotonin regulation (green), inflammation (red) and metabolism (blue), effects which are shown as purple arrows. GC, glucocorticoids; ACTH, adrenocorticotropic hormone; CRH, corticotropin releasing hormone; 5HT, serotonin; Trp, tryptophan; IDO, indolamine-2,3-dioxygenase; KA, kynuric acid; QA, quinolinic acid; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; BDNF, brain derived neurotrophic factor; DAMPs, danger associated molecular patterns; MAMPs, microbe associated molecular patterns; PPARγ, peroxisome proliferator activated receptor gamma; GSKβ, glycogen synthase kinase 3 beta; InR, insulin receptor; AKT, Protein kinase B; AMPK, 5′ AMP-activated protein kinase; PGC1, proliferator-activated receptor gamma coactivator; UCP2, uncoupling protein 2; ROS, reactive oxygen species.

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