Dietary ellagic acid therapy for CNS autoimmunity: Targeting on Alloprevotella rava and propionate metabolism.

IF 13.8 1区生物学 Q1 MICROBIOLOGY

Microbiome Pub Date : 2024-06-24 DOI:10.1186/s40168-024-01819-8

Bing Han, Lin Shi, Ming-Yue Bao, Feng-Lin Yu, Yan Zhang, Xin-Yu Lu, Yang Wang, Dong-Xiao Li, Jing-Chao Lin, Wei Jia, Xing Li, Yuan Zhang

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引用次数: 0

Abstract

Background: Mediterranean diet rich in polyphenolic compounds holds great promise to prevent and alleviate multiple sclerosis (MS), a central nervous system autoimmune disease associated with gut microbiome dysbiosis. Health-promoting effects of natural polyphenols with low bioavailability could be attributed to gut microbiota reconstruction. However, its underlying mechanism of action remains elusive, resulting in rare therapies have proposed for polyphenol-targeted modulation of gut microbiota for the treatment of MS.

Results: We found that oral ellagic acid (EA), a natural polyphenol rich in the Mediterranean diet, effectively halted the progression of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, via regulating a microbiota-metabolites-immunity axis. EA remodeled the gut microbiome composition and particularly increased the relative abundances of short-chain fatty acids -producing bacteria like Alloprevotella. Propionate (C3) was most significantly up-regulated by EA, and integrative modeling revealed a strong negative correlation between Alloprevotella or C3 and the pathological symptoms of EAE. Gut microbiota depletion negated the alleviating effects of EA on EAE, whereas oral administration of Alloprevotella rava mimicked the beneficial effects of EA on EAE. Moreover, EA directly promoted Alloprevotella rava (DSM 22548) growth and C3 production in vitro. The cell-free supernatants of Alloprevotella rava co-culture with EA suppressed Th17 differentiation by modulating acetylation in cell models. C3 can alleviate EAE development, and the mechanism may be through inhibiting HDAC activity and up-regulating acetylation thereby reducing inflammatory cytokines secreted by pathogenic Th17 cells.

Conclusions: Our study identifies EA as a novel and potentially effective prebiotic for improving MS and other autoimmune diseases via the microbiota-metabolites-immunity axis. Video Abstract.

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中枢神经系统自身免疫的鞣花酸饮食疗法：鞣花酸治疗中枢神经系统自身免疫病：以酵母菌和丙酸代谢为靶点。

背景：多发性硬化症（MS）是一种与肠道微生物群失调有关的中枢神经系统自身免疫性疾病。生物利用率低的天然多酚对健康的促进作用可归因于肠道微生物群的重建。然而，其潜在的作用机制仍然难以捉摸，因此很少有人提出用多酚靶向调节肠道微生物群来治疗多发性硬化症：我们发现，地中海饮食中富含的天然多酚鞣花酸（EA）可通过调节微生物群-代谢物-免疫轴，有效阻止多发性硬化症动物模型实验性自身免疫性脑脊髓炎（EAE）的进展。EA 重塑了肠道微生物群的组成，尤其增加了产生短链脂肪酸的细菌（如 Alloprevotella）的相对丰度。EA对丙酸盐（C3）的上调最为明显，综合建模显示，Alloprevotella或C3与EAE的病理症状之间存在很强的负相关。肠道微生物群耗竭抵消了EA对EAE的缓解作用，而口服Alloprevotella rava则模拟了EA对EAE的有益作用。此外，EA直接促进了Alloprevotella rava（DSM 22548）在体外的生长和C3的产生。Alloprevotella rava与EA共培养的无细胞上清液通过调节细胞模型中的乙酰化抑制了Th17的分化。C3可以缓解EAE的发展，其机制可能是通过抑制HDAC活性和上调乙酰化从而减少致病性Th17细胞分泌的炎性细胞因子：我们的研究发现 EA 是一种新型的、潜在有效的益生元，可通过微生物群-代谢物-免疫轴改善多发性硬化症和其他自身免疫性疾病。视频摘要

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来源期刊

Microbiome MICROBIOLOGY-

CiteScore

21.90

自引率

2.60%

发文量

198

审稿时长

4 weeks

期刊介绍： Microbiome is a journal that focuses on studies of microbiomes in humans, animals, plants, and the environment. It covers both natural and manipulated microbiomes, such as those in agriculture. The journal is interested in research that uses meta-omics approaches or novel bioinformatics tools and emphasizes the community/host interaction and structure-function relationship within the microbiome. Studies that go beyond descriptive omics surveys and include experimental or theoretical approaches will be considered for publication. The journal also encourages research that establishes cause and effect relationships and supports proposed microbiome functions. However, studies of individual microbial isolates/species without exploring their impact on the host or the complex microbiome structures and functions will not be considered for publication. Microbiome is indexed in BIOSIS, Current Contents, DOAJ, Embase, MEDLINE, PubMed, PubMed Central, and Science Citations Index Expanded.

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