• ①納入783名有1型糖尿病（T1D）遺傳風險的白人兒童，分析糞便宏基因組的縱向變化，并進行巢式病例對照分析；
• ②對照兒童菌群中，與細菌發酵和短鏈脂肪酸生物合成相關的基因含量更高，但未鑒定出具有普遍性的與胰島自身免疫或 T1D顯著相關的菌群成員；
• ③嬰兒腸道菌群發育呈現動態變化和個體差異，出生第一年內以雙歧桿菌屬（兩歧/短/長雙歧桿菌）或變形菌門為優勢菌；
• ④含有利用人乳寡糖基因的長雙歧桿菌菌株，特異存在于母乳喂養嬰兒中。

1型糖尿病（T1D）是一種自身免疫疾病，與遺傳和環境因素有關。TEDDY研究是一項美國和歐洲的多中心縱向隊列研究，分析有T1D遺傳風險的嬰幼兒的腸道菌群等潛在T1D風險因素。Nature剛剛上線兩項基于該隊列的研究，本研究主要分析了與T1D相關的腸道菌群功能和組成特征，表明短鏈脂肪酸對T1D有潛在預防作用。該研究也分析了嬰幼兒期腸道菌群發育的規律。

The human gut microbiome in early-onset type 1 diabetes from the TEDDY study

TEDDY研究中早發1型糖尿病中的人體腸道菌群

Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors, including complex genetic elements, patient exposures and the gut microbiome. Viral infections and broader gut dysbioses have been identified as potential causes or contributing factors; however, human studies have not yet identified microbial compositional or functional triggers that are predictive of islet autoimmunity or T1D. Here we analyse 10,913 metagenomes in stool samples from 783 mostly white, non-Hispanic children. The samples were collected monthly from three months of age until the clinical end point (islet autoimmunity or T1D) in the The Environmental Determinants of Diabetes in the Young (TEDDY) study, to characterize the natural history of the early gut microbiome in connection to islet autoimmunity, T1D diagnosis, and other common early life events such as antibiotic treatments and probiotics. The microbiomes of control children contained more genes that were related to fermentation and the biosynthesis of short-chain fatty acids, but these were not consistently associated with particular taxa across geographically diverse clinical centres, suggesting that microbial factors associated with T1D are taxonomically diffuse but functionally more coherent. When we investigated the broader establishment and development of the infant microbiome, both taxonomic and functional profiles were dynamic and highly individualized, and dominated in the first year of life by one of three largely exclusive Bifidobacterium species (B. bifidum, B. breve or B. longum) or by the phylum Proteobacteria. In particular, the strain-specific carriage of genes for the utilization of human milk oligosaccharide within a subset of B. longum was present specifically in breast-fed infants. These analyses of TEDDY gut metagenomes provide, to our knowledge, the largest and most detailed longitudinal functional profile of the developing gut microbiome in relation to islet autoimmunity, T1D and other early childhood events. Together with existing evidence from human cohorts and a T1D mouse model, these data support the protective effects of short-chain fatty acids in early-onset human T1D.

First Authors:
Tommi Vatanen

Correspondence Authors:
Curtis Huttenhower,Ramnik J Xavier

All Authors:
Tommi Vatanen,Eric A Franzosa,Randall Schwager,Surya Tripathi,Timothy D Arthur,Kendra Vehik,?ke Lernmark,William A Hagopian,Marian J Rewers,Jin-Xiong She,Jorma Toppari,Anette-G Ziegler,Beena Akolkar,Jeffrey P Krischer,Christopher J Stewart,Nadim J Ajami,Joseph F Petrosino,Dirk Gevers,Harri L?hdesm?ki,Hera Vlamakis,Curtis Huttenhower,Ramnik J Xavier