维生素A、膳食纤维和微生物-肠-脑轴之间的协同相互作用:预防阿尔茨海默病的潜在机制。

IF 3.3 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Shadt Skawratananond, Grace E McCrea, Paul Lie, Matthew B Buxton, Sean P Daly, Nicholas A Vojtkofsky, Shane C Smith, Charlie Zhang, Matthew Hernandez, Ashly Hindle, Aric F Logsdon, J Josh Lawrence
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引用次数: 0

摘要

人类胃肠道拥有庞大而多样的微生物群落,肠道微生物组在许多影响整体健康和疾病进展的生物过程中发挥着重要作用。新出现的证据已经在阿尔茨海默病(AD)患者的海马体中发现了细菌脂多糖,强调了胃肠道、肠道微生物群、中枢和肠神经系统之间的复杂关系——通常被称为“微生物-肠-脑轴”。在这篇综述中,我们探讨了微生物-肠-脑轴在AD发病中的作用机制。我们提出,充分水平的全反式维甲酸(ATRA),维生素A的生物活性形式,通过上调紧密连接蛋白和通过诱导调节性t细胞分化调节免疫功能来增强肠道屏障的完整性,从而减轻炎症。此外,膳食纤维通过细菌发酵促进短链脂肪酸(如丁酸盐)的产生,从而补充了这一过程。反过来,丁酸盐作为组蛋白去乙酰化酶抑制剂,通过提高醛脱氢酶基因表达来上调ATRA的生物利用度。我们的机制框架得到了阿尔茨海默病内毒素假说的支持,该假说认为感染性病原体穿过血脑屏障的运动导致神经炎症的恶性循环,这是阿尔茨海默病发病的关键因素,导致淀粉样蛋白沉积、小胶质细胞激活和cyp26a1介导的ATRA降解。最后,我们讨论了基于微生物组的治疗策略和饮食干预,包括益生元化合物,益生菌,粪便微生物群移植,MIND饮食,以及由维生素a /D和膳食纤维组成的组合方法,作为通过微生物-肠-脑轴缓解AD进展的潜在方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The synergistic interplay between vitamin A, dietary fiber, and the microbiota-gut-brain axis: a potential mechanism for preventing Alzheimer's disease.

The human gastrointestinal tract harbors a vast and diverse microbial community, with the gut microbiome playing a fundamental role in numerous biological processes that influence overall health and disease progression. Emerging evidence has identified bacterial lipopolysaccharides in the hippocampus of patients with Alzheimer's disease (AD), highlighting the intricate relationship between the gastrointestinal tract, gut microbiome, and the central and enteric nervous systems-commonly referred to as the "microbiota-gut-brain axis." In this review, we explore the mechanisms by which the microbiota-gut-brain axis contributes to AD pathogenesis. We propose that sufficient levels of all-trans retinoic acid (ATRA), the bioactive form of vitamin A, enhance intestinal barrier integrity by upregulating tight junction proteins and modulating immune function through the induction of regulatory T-cell differentiation, thereby mitigating inflammation. Furthermore, dietary fiber complements this process by promoting the production of short-chain fatty acids, such as butyrate, via bacterial fermentation. Butyrate, in turn, acts as a histone deacetylase inhibitor, upregulating ATRA bioavailability by elevating aldehyde dehydrogenase gene expression. Our mechanistic framework is supported by the endotoxin hypothesis of AD, which maintains that the movement of infectious pathogens across the blood-brain barrier causes a vicious cycle of inflammation, a key factor of AD pathogenesis, leading to amyloid-β deposition, microglial activation, and CYP26A1-mediated ATRA degradation. Finally, we discuss microbiome-based therapeutic strategies and dietary interventions, including prebiotic compounds, probiotic bacteria, fecal microbiota transplantation, the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, and a combined approach featuring vitamins A/D and dietary fiber, as potential approaches to prevent progression to AD via the microbiota-gut-brain axis.

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来源期刊
CiteScore
9.40
自引率
2.20%
发文量
104
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Gastrointestinal and Liver Physiology publishes original articles pertaining to all aspects of research involving normal or abnormal function of the gastrointestinal tract, hepatobiliary system, and pancreas. Authors are encouraged to submit manuscripts dealing with growth and development, digestion, secretion, absorption, metabolism, and motility relative to these organs, as well as research reports dealing with immune and inflammatory processes and with neural, endocrine, and circulatory control mechanisms that affect these organs.
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