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探讨微生物 SCFAs 对肠道耐受和食物过敏的保护作用的分子机制。

Exploring the Molecular Mechanisms Underlying the Protective Effects of Microbial SCFAs on Intestinal Tolerance and Food Allergy.

机构信息

Biomedical Research Center, Institute for Medical Microbiology and Hygiene, Philipps-University Marburg, Marburg, Germany.

出版信息

Front Immunol. 2020 Jun 16;11:1225. doi: 10.3389/fimmu.2020.01225. eCollection 2020.


DOI:10.3389/fimmu.2020.01225
PMID:32612610
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7308428/
Abstract

A body of evidence suggests that food allergy (FA) has increased in prevalence over the past few decades. Novel findings support the hypothesis that some commensal bacteria and particularly microbial metabolites might contribute to development of oral tolerance and prevention from FA. Recently, beneficial effects of short-chain fatty acids (SCFAs), the main class of gut microbiota-derived metabolites, on FA have been proposed. The intestinal SCFAs are major end products during bacterial fermentation of complex and non-digestible carbohydrates such as dietary fiber. The multifaceted mechanisms underlying beneficial effects of SCFAs on the mucosal immune system comprise the regulation of diverse cellular pathways in epithelial, dendritic, and T cells, as well as the impact on the immunometabolism and epigenetic status of regulatory lymphocytes. Of note, SCFAs are effective inhibitors of histone deacetylases (HDACs). As a consequence, SCFAs appear to be implicated in attenuation of intestinal inflammation and autoimmune diseases. In this review, we will discuss the recent development in this research area by highlighting the role of the individual SCFAs acetate, propionate, butyrate, and pentanoate in promoting the differentiation of regulatory T and B cells and their potential beneficial effects on the prevention of FA. In this context, targeted alterations in the gut microbiota in favor of SCFA producers or supplementation of medicinal food enriched in SCFAs could be a novel therapeutic concept for FA.

摘要

有大量证据表明,食物过敏(FA)的患病率在过去几十年中有所增加。新的发现支持了这样一种假设,即一些共生细菌,特别是微生物代谢物,可能有助于口腔耐受的发展和预防 FA。最近,短链脂肪酸(SCFAs)对 FA 的有益作用被提出。肠道 SCFAs 是肠道微生物群衍生代谢物的主要类别,是细菌发酵复杂和不可消化的碳水化合物(如膳食纤维)的主要终产物。SCFAs 对黏膜免疫系统的有益作用的多方面机制包括对上皮细胞、树突状细胞和 T 细胞中不同细胞途径的调节,以及对调节性淋巴细胞的免疫代谢和表观遗传状态的影响。值得注意的是,SCFAs 是组蛋白去乙酰化酶(HDACs)的有效抑制剂。因此,SCFAs 似乎与肠道炎症和自身免疫性疾病的减轻有关。在这篇综述中,我们将通过强调个体 SCFAs(乙酸盐、丙酸盐、丁酸盐和戊酸盐)在促进调节性 T 和 B 细胞分化及其对预防 FA 的潜在有益作用方面的作用,讨论这一研究领域的最新进展。在这方面,有利于 SCFA 产生菌的肠道微生物群的靶向改变或富含 SCFAs 的药用食品的补充可能是 FA 的一种新的治疗概念。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc85/7308428/1220a31eabb5/fimmu-11-01225-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc85/7308428/1220a31eabb5/fimmu-11-01225-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc85/7308428/1220a31eabb5/fimmu-11-01225-g0001.jpg

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[1]
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[2]
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[4]
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[5]
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[6]
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[3]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism.

Cell. 2020-3-10

[2]
Origins and clonal convergence of gastrointestinal IgE B cells in human peanut allergy.

Sci Immunol. 2020-3-6

[3]
Butyrate inhibits human mast cell activation via epigenetic regulation of FcεRI-mediated signaling.

Allergy. 2020-8

[4]
Chromatin dynamics and histone modifications in intestinal microbiota-host crosstalk.

Mol Metab. 2020-8

[5]
Dietary Antigens Induce Germinal Center Responses in Peyer's Patches and Antigen-Specific IgA Production.

Front Immunol. 2019-10-15

[6]
Short-chain fatty acids: Bacterial messengers modulating the immunometabolism of T cells.

Eur J Immunol. 2019-5-17

[7]
Intestinal development and homeostasis require activation and apoptosis of diet-reactive T cells.

J Clin Invest. 2019-4-2

[8]
The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes.

Nat Commun. 2019-2-15

[9]
Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers.

mBio. 2019-1-29

[10]
An Insight Into the Intestinal Web of Mucosal Immunity, Microbiota, and Diet in Inflammation.

Front Immunol. 2018-11-20

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