Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Unit, Cape Town, South Africa.
Department of Pharmacology and Toxicology, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain; Biomedical Network Research Center of Mental Health (CIBERSAM), Institute of Health Carlos III, Madrid, Spain; Neurochemistry Research Institute UCM, Hospital 12 de Octubre Research Institute (Imas12), Madrid, Spain.
J Neuroimmunol. 2023 Sep 15;382:578155. doi: 10.1016/j.jneuroim.2023.578155. Epub 2023 Jul 25.
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.
在这篇叙述性评论中，我们研究了肠道菌群失调、神经炎症与应激相关疾病（包括抑郁症、焦虑症和创伤后应激障碍（PTSD））之间的关联，并探讨了色氨酸（TRP）代谢和血小板是否在其中发挥作用。应激相关疾病的发病机制复杂，尚未完全阐明。然而，在 TRP 代谢和血小板中，可能潜在地发现慢性炎症与这些疾病之间的联系。通过批判性地分析现有关于血小板、肠道微生物组与应激相关疾病的文献，我们希望阐明血小板在调节对 5-羟色胺（5-HT）水平和神经炎症的影响方面的作用。我们纳入了专门研究血小板和 TRP 代谢与炎症、神经炎症和神经精神疾病之间关系的研究。应激引起的微生物组成改变可能导致肠道通透性增加，促进微生物产物易位，并触发促炎细胞因子的释放。这导致血小板变得过度活跃，并将 5-HT 分泌到血浆中。促炎细胞因子水平的增加也可能导致血脑屏障（BBB）通透性增加，允许炎症介质进入大脑，影响 TRP 代谢产物（如 5-HT、犬尿氨酸（KYNA）和喹啉酸（QUIN））的平衡。这些改变可能导致神经炎症和可能的神经损伤。此外，血小板可以穿过受损的 BBB 并与星形胶质细胞和神经元相互作用，导致 5-HT 和促炎因子的分泌，从而加剧大脑中的炎症状态。外周炎症引起的神经炎症的机制尚不清楚，但大脑和肠道通过血液的联系可能很重要。确定反映神经炎症的血浆中与外周炎症相关的外周生物标志物和机制可能很重要。本综述为进一步研究肠道微生物组、血液微生物组与神经精神疾病之间的关联奠定了基础。将这些发现与血液中的蛋白质和代谢物标志物相结合，可能会扩展我们对这一主题的理解。
