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. 2022 May 18;14(10):2111. doi: 10.3390/nu14102111

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Potential microbiome–gut–brain communication pathways modulated by polyphenols in mental disorders. Gut microorganisms metabolize polyphenols to potentially active metabolites. Polyphenols and their metabolites support the rebalancing of the altered gut microbiome during dysbiosis, and the metabolites can cross the intestinal epithelium and reach the systemic circulation and brain. These molecules may modulate gut–brain communication via neural (blue letters), immune (pink letters), and humoral/metabolic (green letters) pathways. Polyphenols and their metabolites can modulate vagus nerve communication, the HPA axis, pro-inflammatory mediators, neurotrophic factors, and serotonin levels, positively influencing brain functions. Polyphenols have antioxidant effects and can reduce ROS levels in brain disorders [27,220,250], and they can also stimulate gut microbiome production of SCFAs [251]. Furthermore, polyphenols and their metabolites may have local brain effects such as improved cerebrovascular blood flow and a reduction in neuroinflammation [252]. The major gut–brain mechanisms by which polyphenols may exert beneficial effects are indicated with red arrows ( activation/upregulation, inhibition/downregulation). BBB: blood–brain barrier; IDO: indolamine 2,3 dioxygenase; TDO: tryptophan 2,3-dioxygenase; QA: quinolinic acid; PPARγ: peroxisome proliferator-activated receptor gamma; AMPK: 5′AMP-activated protein kinase; ROS: reactive oxygen species; TOR: target of rapamycin; ⊕: stimulates/promotes.

Inline graphic — Potential microbiome–gut–brain communication pathways modulated by polyphenols in mental disorders. Gut microorganisms metabolize polyphenols to potentially active metabolites. Polyphenols and their metabolites support the rebalancing of the altered gut microbiome during dysbiosis, and the metabolites can cross the intestinal epithelium and reach the systemic circulation and brain. These molecules may modulate gut–brain communication via neural (blue letters), immune (pink letters), and humoral/metabolic (green letters) pathways. Polyphenols and their metabolites can modulate vagus nerve communication, the HPA axis, pro-inflammatory mediators, neurotrophic factors, and serotonin levels, positively influencing brain functions. Polyphenols have antioxidant effects and can reduce ROS levels in brain disorders [27,220,250], and they can also stimulate gut microbiome production of SCFAs [251]. Furthermore, polyphenols and their metabolites may have local brain effects such as improved cerebrovascular blood flow and a reduction in neuroinflammation [252]. The major gut–brain mechanisms by which polyphenols may exert beneficial effects are indicated with red arrows ( activation/upregulation, inhibition/downregulation). BBB: blood–brain barrier; IDO: indolamine 2,3 dioxygenase; TDO: tryptophan 2,3-dioxygenase; QA: quinolinic acid; PPARγ: peroxisome proliferator-activated receptor gamma; AMPK: 5′AMP-activated protein kinase; ROS: reactive oxygen species; TOR: target of rapamycin; ⊕: stimulates/promotes.