Kurhaluk Natalia, Kamiński Piotr, Bilski Rafał, Kołodziejska Renata, Woźniak Alina, Tkaczenko Halina
Institute of Biology, Pomeranian University in Słupsk, Arciszewski St. 22 B, 76-200 Słupsk, Poland.
Department of Medical Biology and Biochemistry, Division of Ecology and Environmental Protection, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Skłodowska-Curie St. 9, 85-094 Bydgoszcz, Poland.
Int J Mol Sci. 2025 Apr 12;26(8):3658. doi: 10.3390/ijms26083658.
This narrative review presents the role of antioxidants in regulating the gut microbiota and the impact on the gut-brain axis, with a particular focus on neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). These diseases are characterised by cognitive decline, motor dysfunction, and neuroinflammation, all of which are significantly exacerbated by oxidative stress. This review elucidates the contribution of oxidative damage to disease progression and explores the potential of antioxidants to mitigate these pathological processes through modulation of the gut microbiota and associated pathways. Based on recent studies retrieved from reputable databases, including PubMed, Web of Science, and Scopus, this article outlines the mechanisms by which antioxidants influence gut health and exert neuroprotective effects. Specifically, it discusses how antioxidants, including polyphenols, vitamins, and flavonoids, contribute to the reduction in reactive oxygen species (ROS) production and neuroinflammation, thereby promoting neuronal survival and minimising oxidative damage in the brain. In addition, the article explores the role of antioxidants in modulating key molecular pathways involved in oxidative stress and neuroinflammation, such as the NF-κB, Nrf2, MAPK, and PI3K/AKT pathways, which regulate ROS generation, inflammatory cytokine expression, and antioxidant responses essential for maintaining cellular homeostasis in both the gut and the central nervous system. In addition, this review explores the complex relationship between gut-derived metabolites, oxidative stress, and neurodegenerative diseases, highlighting how dysbiosis-an imbalance in the gut microbiota-can exacerbate oxidative stress and contribute to neuroinflammation, thereby accelerating the progression of such diseases as AD and PD. The review also examines the role of short-chain fatty acids (SCFAs) produced by beneficial gut bacteria in modulating these pathways to attenuate neuroinflammation and oxidative damage. Furthermore, the article explores the therapeutic potential of microbiota-targeted interventions, including antioxidant delivery by probiotics and prebiotics, as innovative strategies to restore microbial homeostasis and support brain health. By synthesising current knowledge on the interplay between antioxidants, the gut-brain axis, and the molecular mechanisms underlying neurodegeneration, this review highlights the therapeutic promise of antioxidant-based interventions in mitigating oxidative stress and neurodegenerative disease progression. It also highlights the need for further research into antioxidant-rich dietary strategies and microbiota-focused therapies as promising avenues for the prevention and treatment of neurodegenerative diseases.
本叙述性综述介绍了抗氧化剂在调节肠道微生物群中的作用以及对肠-脑轴的影响，特别关注神经退行性疾病，如阿尔茨海默病（AD）和帕金森病（PD）。这些疾病的特征是认知能力下降、运动功能障碍和神经炎症，所有这些都会因氧化应激而显著加剧。本综述阐明了氧化损伤对疾病进展的作用，并探讨了抗氧化剂通过调节肠道微生物群及相关途径来减轻这些病理过程的潜力。基于从包括PubMed、科学网和Scopus在内的知名数据库检索到的最新研究，本文概述了抗氧化剂影响肠道健康并发挥神经保护作用的机制。具体而言，它讨论了包括多酚、维生素和黄酮类化合物在内的抗氧化剂如何有助于减少活性氧（ROS）的产生和神经炎症，从而促进神经元存活并将大脑中的氧化损伤降至最低。此外，本文探讨了抗氧化剂在调节参与氧化应激和神经炎症的关键分子途径中的作用，如NF-κB、Nrf2、MAPK和PI3K/AKT途径，这些途径调节ROS生成、炎症细胞因子表达以及维持肠道和中枢神经系统细胞内稳态所必需的抗氧化反应。此外，本综述探讨了肠道衍生代谢物、氧化应激和神经退行性疾病之间的复杂关系，强调了肠道微生物群失衡——肠道微生物群失调——如何加剧氧化应激并导致神经炎症，从而加速AD和PD等疾病进程。该综述还研究了有益肠道细菌产生的短链脂肪酸（SCFAs）在调节这些途径以减轻神经炎症和氧化损伤中的作用。此外，本文探讨了以微生物群为靶点的干预措施的治疗潜力，包括通过益生菌和益生元递送抗氧化剂，作为恢复微生物稳态和支持大脑健康的创新策略。通过综合当前关于抗氧化剂、肠-脑轴和神经退行性变潜在分子机制之间相互作用的知识，本综述强调了基于抗氧化剂的干预措施在减轻氧化应激和神经退行性疾病进展方面的治疗前景。它还强调了有必要进一步研究富含抗氧化剂的饮食策略和以微生物群为重点的疗法，将其作为预防和治疗神经退行性疾病的有前景途径。
