Islet autoantibody seroconversion in type-1 diabetes is associated with metagenome-assembled genomes in infant gut microbiomes.
Islet autoantibody seroconversion in type-1 diabetes is associated with metagenome-assembled genomes in infant gut microbiomes.
复制标题
1 型糖尿病中的胰岛自身抗体血清转化与婴儿肠道微生物组中宏基因组组装的基因组相关。
DOI：
10.1038/s41467-022-31227-1
复制
发表时间：
2022-06-21
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
某些遗传易感儿童的免疫系统可被某些环境因素触发，产生针对胰腺β细胞的胰岛自身抗体（IA），这大大增加了他们患1型糖尿病的风险。正在积极研究的环境因素是肠道微生物组，因为它在免疫系统教育中起着重要作用。在这里，我们研究了在年轻人糖尿病环境决定因素（TEDDY）项目中887名高危儿童中重新组装的肠道宏基因组。我们的结果揭示了一小组核心蛋白家族，存在于>50%的受试者中，占测序读数的64%。时间序列分箱从883个物种中产生了21，536个高质量的宏基因组组装基因组（MAG），其中包括176个物种，这些物种迄今为止在以前的全面人类微生物组调查中没有MAG代表。IA血清转换与2373个MAG正相关，与1549个MAG负相关。比较基因组学分析鉴定拟杆菌MAG中的脂多糖生物合成和厌氧柄菌MAG中的硫酸盐还原作为具有正IA关联的MAG的功能特征。具有负IA-缔合的MAG中的功能特征包括乳酸菌MAG中的碳水化合物降解和大肠杆菌MAG中的硝酸盐还原。总的来说，我们的研究结果显示了一组与IA血清转化相关的独特肠道微生物，并揭示了这些IA相关微生物的功能基因组学特征。在这里，通过表征TEDDY项目中高危儿童的肠道宏基因组，作者将导致1型糖尿病的自身免疫的发生与肠道微生物群中的某些微生物相关联，并确定这些微生物基因组中编码的代谢能力，这些代谢能力为这种关联提供了功能性见解。
The immune system of some genetically susceptible children can be triggered by certain environmental factors to produce islet autoantibodies (IA) against pancreatic β cells, which greatly increases their risk for Type-1 diabetes. An environmental factor under active investigation is the gut microbiome due to its important role in immune system education. Here, we study gut metagenomes that are de-novo-assembled in 887 at-risk children in the Environmental Determinants of Diabetes in the Young (TEDDY) project. Our results reveal a small set of core protein families, present in >50% of the subjects, which account for 64% of the sequencing reads. Time-series binning generates 21,536 high-quality metagenome-assembled genomes (MAGs) from 883 species, including 176 species that hitherto have no MAG representation in previous comprehensive human microbiome surveys. IA seroconversion is positively associated with 2373 MAGs and negatively with 1549 MAGs. Comparative genomics analysis identifies lipopolysaccharides biosynthesis in Bacteroides MAGs and sulfate reduction in Anaerostipes MAGs as functional signatures of MAGs with positive IA-association. The functional signatures in the MAGs with negative IA-association include carbohydrate degradation in lactic acid bacteria MAGs and nitrate reduction in Escherichia MAGs. Overall, our results show a distinct set of gut microorganisms associated with IA seroconversion and uncovered the functional genomics signatures of these IA-associated microorganisms Here, by characterizing gut metagenomes of at-risk children in the TEDDY project, the authors associate onset of autoimmunity leading to Type-1 diabetes with certain sets of microorganisms in the gut microbiota, and identify metabolic capabilities encoded in the genomes of these microorganisms that provide functional insights to the association.
登录
查看更多内容
影响因子：
14.9
作者：
Chen IA;Chu K;Palaniappan K;Pillay M;Ratner A;Huang J;Huntemann M;Varghese N;White JR;Seshadri R;Smirnova T;Kirton E;Jungbluth SP;Woyke T;Eloe-Fadrosh EA;Ivanova NN;Kyrpides NC
通讯作者：
Kyrpides NC
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.2
作者：
Bahadoran Z;Ghasemi A;Mirmiran P;Azizi F;Hadaegh F
通讯作者：
Hadaegh F
DOI：
10.1152/ajpendo.00302.2006
发表时间：
2007-03-01
影响因子：
5.1
作者：
Creely, S. J.;McTernan, P. G.;Kumar, S.
通讯作者：
Kumar, S.
影响因子：
6.8
作者：
Edwards, Thea M.;Hamlin, Heather J.;Guillette, Louis J., Jr.
通讯作者：
Guillette, Louis J., Jr.