Towards a functional hypothesis relating anti-islet cell autoimmunity to the dietary impact on microbial communities and butyrate production.
Towards a functional hypothesis relating anti-islet cell autoimmunity to the dietary impact on microbial communities and butyrate production.
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DOI：
10.1186/s40168-016-0163-4
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发表时间：
2016-04-26
期刊：
影响因子：
15.5
通讯作者：
zu Castell W
中科院分区：
文献类型：
--
作者：
Endesfelder D;Engel M;Davis-Richardson AG;Ardissone AN;Achenbach P;Hummel S;Winkler C;Atkinson M;Schatz D;Triplett E;Ziegler AG;zu Castell W
抗胰岛细胞自身免疫的发展先于临床1型糖尿病，并发生在生命的非常早期。在这一早期阶段，饮食因素强烈影响肠道微生物群的组成。同时，肠道微生物群在婴儿免疫系统的发育中起着核心作用。饮食、微生物群落和抗胰岛细胞自身免疫发展之间的关系的功能模型可以为肠道微生物群在1型糖尿病发病机制中的作用提供重要的新见解。发展了一种新的方法，能够在单个微生物分类群和分析整个微生物种群的经典生态指标之间的聚集水平上分析微生物组。在胰岛自身抗体形成之前，估计微生物共生网络在6个月大时被用来确定功能性微生物群落的候选。根据这些社区对儿童进行分层，揭示了饮食、肠道微生物群和胰岛自身抗体发展之间的功能关联。两个社区分别与母乳喂养和固体食物引进密切相关。第三个群体揭示了以类杆菌为主的儿童亚组，而两个亚组则以低类杆菌和阿克曼藻类丰富度为主。以类杆菌为主的亚群的特点是早期引入非牛奶饮食，增加早期自身抗体产生的风险，以及通过醋酸酯共发酵产生丁酸盐的基因丰度较低。通过结合我们的结果和文献中的信息，我们为丁酸盐在1型糖尿病发病机制中的保护作用提供了一个完善的功能假说。基于从共生网络估计的微生物群落的功能特征，我们提供了证据，表明粘蛋白降解菌组成的变化与抗胰岛细胞自身免疫的早期发展有关。我们假设，较低的类杆菌水平有利于提高阿克曼氏菌的水平，从而导致乙酸菌与硫酸盐还原细菌相比具有竞争优势，从而通过醋酸酯的联合发酵增加丁酸盐的产量。这一假说表明，丁酸盐对胰岛细胞自身抗体的产生具有保护作用。本文的在线版本(doi：10.1186/s40168.0163.0163-4)包含补充材料，授权用户可以使用。
The development of anti-islet cell autoimmunity precedes clinical type 1 diabetes and occurs very early in life. During this early period, dietary factors strongly impact on the composition of the gut microbiome. At the same time, the gut microbiome plays a central role in the development of the infant immune system. A functional model of the association between diet, microbial communities, and the development of anti-islet cell autoimmunity can provide important new insights regarding the role of the gut microbiome in the pathogenesis of type 1 diabetes. A novel approach was developed to enable the analysis of the microbiome on an aggregation level between a single microbial taxon and classical ecological measures analyzing the whole microbial population. Microbial co-occurrence networks were estimated at age 6 months to identify candidates for functional microbial communities prior to islet autoantibody development. Stratification of children based on these communities revealed functional associations between diet, gut microbiome, and islet autoantibody development. Two communities were strongly associated with breast-feeding and solid food introduction, respectively. The third community revealed a subgroup of children that was dominated by Bacteroides abundances compared to two subgroups with low Bacteroides and increased Akkermansia abundances. The Bacteroides-dominated subgroup was characterized by early introduction of non-milk diet, increased risk for early autoantibody development, and by lower abundances of genes for the production of butyrate via co-fermentation of acetate. By combining our results with information from the literature, we provide a refined functional hypothesis for a protective role of butyrate in the pathogenesis of type 1 diabetes. Based on functional traits of microbial communities estimated from co-occurrence networks, we provide evidence that alterations in the composition of mucin degrading bacteria associate with early development of anti-islet cell autoimmunity. We hypothesize that lower levels of Bacteroides in favor of increased levels of Akkermansia lead to a competitive advantage of acetogens compared to sulfate reducing bacteria, resulting in increased butyrate production via co-fermentation of acetate. This hypothesis suggests that butyrate has a protective effect on the development of anti-islet cell autoantibodies. The online version of this article (doi:10.1186/s40168-016-0163-4) contains supplementary material, which is available to authorized users.