Platelets bridging the gap between gut dysbiosis and neuroinflammation in stress-linked disorders: A narrative review.

Rust, Carlien; Malan-Muller, Stefanie; van den Heuvel, Leigh L; Tonge, Daniel; Seedat, Soraya; Pretorius, Etheresia; Hemmings, Sian M J

Abstract

In this narrative review, we examine the association between gut dysbiosis, neuroinflammation, and stress-linked disorders, including depression, anxiety, and post-traumatic stress disorder (PTSD), and investigate whether tryptophan (TRP) metabolism and platelets play a role in this association. The mechanisms underlying the aetiology of stress-linked disorders are complex and not yet completely understood. However, a potential link between chronic inflammation and these disorders may potentially be found in TRP metabolism and platelets. By critically analysing existing literature on platelets, the gut microbiome, and stress-linked disorders, we hope to elicit the role of platelets in mediating the effects on serotonin (5-HT) levels and neuroinflammation. We have included studies specifically investigating platelets and TRP metabolism in relation to inflammation, neuroinflammation and neuropsychiatric disorders. Alteration in microbial composition due to stress could contribute to increased intestinal permeability, facilitating the translocation of microbial products, and triggering the release of pro-inflammatory cytokines. This causes platelets to become hyperactive and secrete 5-HT into the plasma. Increased levels of pro-inflammatory cytokines may also lead to increased permeability of the blood-brain barrier (BBB), allowing inflammatory mediators entry into the brain, affecting the balance of TRP metabolism products, such as 5-HT, kynurenic acid (KYNA), and quinolinic acid (QUIN). These alterations may contribute to neuroinflammation and possible neurological damage. Furthermore, platelets can cross the compromised BBB and interact with astrocytes and neurons, leading to the secretion of 5-HT and pro-inflammatory factors, exacerbating inflammatory conditions in the brain. The mechanisms underlying neuroinflammation resulting from peripheral inflammation are still unclear, but the connection between the brain and gut through the bloodstream could be significant. Identifying peripheral biomarkers and mechanisms in the plasma that reflect neuroinflammation may be important. This review serves as a foundation for further research on the association between the gut microbiome, blood microbiome, and neuropsychiatric disorders. The integration of these findings with protein and metabolite markers in the blood may expand our understanding of the subject. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.]

• Journal Article Type: Article
• Acceptance Date: Jul 23, 2023
• Online Publication Date: Jul 25, 2023
• Publication Date: Sep 15, 2023
• Deposit Date: Aug 22, 2023
• Journal: Journal of neuroimmunology
• Print ISSN: 0165-5728
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 382
• Article Number: 578155
• DOI: https://doi.org/10.1016/j.jneuroim.2023.578155
• Keywords: Gut microbiome, PTSD, Depression, Kynurenine, Serotonin, Tryptophan metabolism, Anxiety