Toward defining the autoimmune microbiome for type 1 diabetes

被引:605
作者
Giongo, Adriana [1 ]
Gano, Kelsey A. [1 ]
Crabb, David B. [1 ]
Mukherjee, Nabanita [2 ]
Novelo, Luis L. [2 ]
Casella, George [2 ]
Drew, Jennifer C. [1 ]
Ilonen, Jorma [3 ,4 ,5 ,6 ,7 ]
Knip, Mikael [7 ,8 ,9 ,10 ]
Hyoty, Heikki [7 ,11 ,12 ]
Veijola, Riitta [7 ,13 ]
Simell, Tuula [7 ,14 ]
Simell, Olli [7 ,14 ]
Neu, Josef [15 ]
Wasserfall, Clive H. [16 ]
Schatz, Desmond [15 ]
Atkinson, Mark A. [16 ]
Triplett, Eric W. [1 ]
机构
[1] Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA
[2] Univ Florida, Dept Stat, Gainesville, FL 32611 USA
[3] Univ Kuopio, Dept Clin Microbiol, FIN-70211 Kuopio, Finland
[4] Univ Turku, Immunogenet Lab, Turku, Finland
[5] Univ Turku, Immunogenet Lab, Oulu, Finland
[6] Univ Turku, Immunogenet Lab, Tampere, Finland
[7] JDRF, Ctr Prevent Type Diabet 1, Turku, Finland
[8] Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland
[9] Tampere Univ Hosp, Dept Pediat, Tampere, Finland
[10] Tampere Univ Hosp, Res Unit, Tampere, Finland
[11] Univ Tampere, Sch Med, Dept Virol, FIN-33101 Tampere, Finland
[12] Tampere Univ Hosp, Ctr Lab Med, Tampere, Finland
[13] Univ Oulu, Dept Pediat, SF-90100 Oulu, Finland
[14] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland
[15] Univ Florida, Dept Pediat, Gainesville, FL 32611 USA
[16] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32611 USA
关键词
Bacteroidetes; Firmicutes; gut microbiota; seroconversion; TREATMENT PARTIALLY PROTECTS; INTESTINAL MICROBIOTA; GUT MICROBIOME; PRONE RAT; IMBALANCES;
D O I
10.1038/ismej.2010.92
中图分类号
Q14 [生态学(生物生态学)];
学科分类号
071012 ; 0713 ;
摘要
Several studies have shown that gut bacteria have a role in diabetes in murine models. Specific bacteria have been correlated with the onset of diabetes in a rat model. However, it is unknown whether human intestinal microbes have a role in the development of autoimmunity that often leads to type 1 diabetes (T1D), an autoimmune disorder in which insulin-secreting pancreatic islet cells are destroyed. High-throughput, culture-independent approaches identified bacteria that correlate with the development of T1D-associated autoimmunity in young children who are at high genetic risk for this disorder. The level of bacterial diversity diminishes overtime in these autoimmune subjects relative to that of age-matched, genotype-matched, nonautoimmune individuals. A single species, Bacteroides ovatus, comprised nearly 24% of the total increase in the phylum Bacteroidetes in cases compared with controls. Conversely, another species in controls, represented by the human firmicute strain CO19, represented nearly 20% of the increase in Firmicutes compared with cases overtime. Three lines of evidence are presented that support the notion that, as healthy infants approach the toddler stage, their microbiomes become healthier and more stable, whereas, children who are destined for autoimmunity develop a microbiome that is less diverse and stable. Hence, the autoimmune microbiome for T1D may be distinctly different from that found in healthy children. These data also suggest bacterial markers for the early diagnosis of T1D. In addition, bacteria that negatively correlated with the autoimmune state may prove to be useful in the prevention of autoimmunity development in high-risk children. The ISME Journal (2011) 5, 82-91; doi:10.1038/ismej.2010.92; published online 8 July 2010
引用
收藏
页码:82 / 91
页数:10
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