Gut-Brain Axis and Neuroinflammation: The Role of Gut Permeability and the Kynurenine Pathway in Neurological Disorders.

IF 3.6 4区 医学 Q3 CELL BIOLOGY Cellular and Molecular Neurobiology Pub Date : 2024-10-08 DOI:10.1007/s10571-024-01496-z
Rowan Kearns
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Abstract

The increasing prevalence of neurological disorders such as Alzheimer's, Parkinson's, and multiple sclerosis presents a significant global health challenge. Despite extensive research, the precise mechanisms underlying these conditions remain elusive, with current treatments primarily addressing symptoms rather than root causes. Emerging evidence suggests that gut permeability and the kynurenine pathway are involved in the pathogenesis of these neurological conditions, offering promising targets for novel therapeutic and preventive strategies. Gut permeability refers to the intestinal lining's ability to selectively allow essential nutrients into the bloodstream while blocking harmful substances. Various factors, including poor diet, stress, infections, and genetic predispositions, can compromise gut integrity, leading to increased permeability. This condition facilitates the translocation of toxins and bacteria into systemic circulation, triggering widespread inflammation that impacts neurological health via the gut-brain axis. The gut-brain axis (GBA) is a complex communication network between the gut and the central nervous system. Dysbiosis, an imbalance in the gut microbiota, can increase gut permeability and systemic inflammation, exacerbating neuroinflammation-a key factor in neurological disorders. The kynurenine pathway, the primary route for tryptophan metabolism, is significantly implicated in this process. Dysregulation of the kynurenine pathway in the context of inflammation leads to the production of neurotoxic metabolites, such as quinolinic acid, which contribute to neuronal damage and the progression of neurological disorders. This narrative review highlights the potential and progress in understanding these mechanisms. Interventions targeting the kynurenine pathway and maintaining a balanced gut microbiota through diet, probiotics, and lifestyle modifications show promise in reducing neuroinflammation and supporting brain health. In addition, pharmacological approaches aimed at modulating the kynurenine pathway directly, such as inhibitors of indoleamine 2,3-dioxygenase, offer potential avenues for new treatments. Understanding and targeting these interconnected pathways are crucial for developing effective strategies to prevent and manage neurological disorders.

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肠脑轴与神经炎症:肠道通透性和犬尿氨酸通路在神经系统疾病中的作用》。
阿尔茨海默氏症、帕金森氏症和多发性硬化症等神经系统疾病的发病率不断上升,给全球健康带来了重大挑战。尽管进行了广泛的研究,但这些疾病的确切机制仍然难以捉摸,目前的治疗方法主要是治标不治本。新的证据表明,肠道通透性和犬尿氨酸途径参与了这些神经系统疾病的发病机制,为新型治疗和预防策略提供了有前景的靶点。肠道通透性是指肠道内壁选择性地允许必需营养物质进入血液,同时阻挡有害物质的能力。包括不良饮食、压力、感染和遗传倾向在内的各种因素都会损害肠道的完整性,导致渗透性增加。这种情况有利于毒素和细菌进入全身循环,引发广泛的炎症,通过肠脑轴影响神经系统健康。肠脑轴(GBA)是肠道和中枢神经系统之间复杂的沟通网络。菌群失调(肠道微生物群失衡)会增加肠道通透性和全身炎症,加剧神经炎症--神经系统疾病的关键因素。色氨酸代谢的主要途径--犬尿氨酸途径与这一过程密切相关。在炎症背景下,犬尿氨酸途径的失调会导致产生神经毒性代谢物,如奎宁酸,从而造成神经元损伤和神经系统疾病的恶化。这篇叙述性综述强调了了解这些机制的潜力和进展。针对犬尿氨酸途径的干预措施以及通过饮食、益生菌和生活方式的改变来维持肠道微生物群平衡的方法有望减少神经炎症并支持大脑健康。此外,旨在直接调节犬尿氨酸途径的药理学方法(如吲哚胺 2,3-二氧化酶抑制剂)也为新的治疗方法提供了潜在的途径。了解并针对这些相互关联的途径,对于制定预防和控制神经系统疾病的有效策略至关重要。
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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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