Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes.
Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes.
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DOI：
10.1371/journal.pone.0025792
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Triplett EW
中科院分区：
文献类型：
--
作者：
Brown CT;Davis-Richardson AG;Giongo A;Gano KA;Crabb DB;Mukherjee N;Casella G;Drew JC;Ilonen J;Knip M;Hyöty H;Veijola R;Simell T;Simell O;Neu J;Wasserfall CH;Schatz D;Atkinson MA;Triplett EW
最近的研究表明，细菌在包括1型糖尿病（T1D）在内的自身免疫性疾病的发展中起作用。在T1D相关自身免疫（即自身抗体）发生时收集的四对匹配的T1D病例对照受试者的粪便样本中，分析了Illumina shotgun宏基因组数据的300多亿个核苷酸碱基。从这些数据中，预测了大约100万个开放阅读框，并与SEED蛋白质数据库进行了比较。在这些样本中发现的3849种功能中，有144种和797种在病例和对照组中更为普遍。参与碳水化合物代谢、黏附、运动、噬菌体、前噬菌体、硫代谢和应激反应的基因在对照组中更为丰富，而参与DNA和蛋白质代谢、有氧呼吸和氨基酸合成的基因在对照组中更为常见。这些数据表明，自身免疫受试者中黏附和鞭毛合成的增加可能参与触发T1D相关的自身免疫反应。代谢潜能的广泛差异表明自身免疫受试者具有功能异常的微生物组。从这些数据集中挖掘16S rRNA数据显示，与病例相比，对照组中产生丁酸盐和黏液降解细菌的比例更高，而那些产生除丁酸盐以外的短链脂肪酸的细菌在病例中更高。因此，丁酸盐合成中一个关键的限速步骤在对照中更为丰富。这些数据表明，健康肠道中产生乳酸和丁酸盐的细菌联合诱导足够数量的粘蛋白合成以维持肠道完整性。相反，非丁酸产生乳酸利用细菌阻止最佳粘蛋白合成，如在自身免疫受试者中发现的。
Recent studies have suggested a bacterial role in the development of autoimmune disorders including type 1 diabetes (T1D). Over 30 billion nucleotide bases of Illumina shotgun metagenomic data were analyzed from stool samples collected from four pairs of matched T1D case-control subjects collected at the time of the development of T1D associated autoimmunity (i.e., autoantibodies). From these, approximately one million open reading frames were predicted and compared to the SEED protein database. Of the 3,849 functions identified in these samples, 144 and 797 were statistically more prevalent in cases and controls, respectively. Genes involved in carbohydrate metabolism, adhesions, motility, phages, prophages, sulfur metabolism, and stress responses were more abundant in cases while genes with roles in DNA and protein metabolism, aerobic respiration, and amino acid synthesis were more common in controls. These data suggest that increased adhesion and flagella synthesis in autoimmune subjects may be involved in triggering a T1D associated autoimmune response. Extensive differences in metabolic potential indicate that autoimmune subjects have a functionally aberrant microbiome. Mining 16S rRNA data from these datasets showed a higher proportion of butyrate-producing and mucin-degrading bacteria in controls compared to cases, while those bacteria that produce short chain fatty acids other than butyrate were higher in cases. Thus, a key rate-limiting step in butyrate synthesis is more abundant in controls. These data suggest that a consortium of lactate- and butyrate-producing bacteria in a healthy gut induce a sufficient amount of mucin synthesis to maintain gut integrity. In contrast, non-butyrate-producing lactate-utilizing bacteria prevent optimal mucin synthesis, as identified in autoimmune subjects.
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影响因子：
5
作者：
Fischer, Curt R.;Tseng, Hsien-Chung;Tai, Mitchell;Prather, Kristala L. J.;Stephanopoulos, Gregory
通讯作者：
Stephanopoulos, Gregory
影响因子：
24.5
作者：
FINNIE, IA;DWARAKANATH, AD;RHODES, JM
通讯作者：
RHODES, JM
影响因子：
4.4
作者：
Lau, Kenneth;Benitez, Patrick;Larkin, Joseph, III
通讯作者：
Larkin, Joseph, III
影响因子：
4.4
作者：
Derrien, Muriel;Collado, M. Carmen;de Vos, Willem M.
通讯作者：
de Vos, Willem M.
DOI：
10.1073/pnas.0706625104
发表时间：
2007-08-21
影响因子：
11.1
作者：
Frank, Daniel N.;Amand, Allison L. St.;Pace, Norman R.
通讯作者：
Pace, Norman R.