Loss of sex and age driven differences in the gut microbiome characterize arthritis-susceptible 0401 mice but not arthritis-resistant 0402 mice.
Loss of sex and age driven differences in the gut microbiome characterize arthritis-susceptible 0401 mice but not arthritis-resistant 0402 mice.
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DOI：
10.1371/journal.pone.0036095
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Taneja V
中科院分区：
文献类型：
--
作者：
Gomez A;Luckey D;Yeoman CJ;Marietta EV;Berg Miller ME;Murray JA;White BA;Taneja V
在人类和转基因小鼠中，HLA-DRB1*0401与易感性有关，而HLA-DRB1*0402与抵抗发生类风湿性关节炎(RA)和胶原诱导性关节炎有关。肠轴对类风湿性关节炎的影响已被提出，但尚未得到证实。我们使用了携带关节炎易感和抗药性的HLA-DR基因的转基因小鼠来探索遗传因素及其与肠道菌群的相互作用是否可以用来预测关节炎的易感性。对DRB1*0401和DRB1*0402转基因小鼠粪便微生物群的16S rRNA基因进行焦糖测序，结果表明*0401转基因小鼠的肠道以类梭状芽孢杆菌为主，而*0402转基因小鼠的肠道富含卟啉单胞菌科和双歧杆菌。DRB1*0402小鼠具有动态的性别和年龄影响的肠道微生物群，而DRB1*0401小鼠即使改变了肠道通透性，也没有表现出年龄和性别差异。RT-PCR检测空肠细胞因子转录产物显示，TH17调节网络基因在*0401和*0402小鼠中的转录水平存在差异。我们首次证明了与肠道微生物组相关的人类白细胞抗原基因可能决定免疫环境，肠道微生物组可能是一个潜在的生物标志物，也可能是关节炎易感性的贡献者。病原共生菌的鉴定将对疾病的发病机制提供新的理解，从而为治疗提供新的方法。
HLA-DRB1*0401 is associated with susceptibility, while HLA-DRB1*0402 is associated with resistance to developing rheumatoid arthritis (RA) and collagen-induced arthritis in humans and transgenic mice respectively. The influence of gut-joint axis has been suggested in RA, though not yet proven. We have used HLA transgenic mice carrying arthritis susceptible and -resistant HLA-DR genes to explore if genetic factors and their interaction with gut flora gut can be used to predict susceptibility to develop arthritis. Pyrosequencing of the 16S rRNA gene from the fecal microbiomes of DRB1*0401 and DRB1*0402 transgenic mice revealed that the guts of *0401 mice is dominated by a Clostridium-like bacterium, whereas the guts of *0402 mice are enriched for members of the Porphyromonadaceae family and Bifidobacteria. DRB1*0402 mice harbor a dynamic sex and age-influenced gut microbiome while DRB1*0401 mice did not show age and sex differences in gut microbiome even though they had altered gut permeability. Cytokine transcripts, measured by rtPCR, in jejuna showed differential TH17 regulatory network gene transcripts in *0401 and *0402 mice. We have demonstrated for the first time that HLA genes in association with the gut microbiome may determine the immune environment and that the gut microbiome might be a potential biomarker as well as contributor for susceptibility to arthritis. Identification of pathogenic commensal bacteria would provide new understanding of disease pathogenesis, thereby leading to novel approaches for therapy.
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DOI：
10.1073/pnas.95.18.10797
发表时间：
1998-09-01
影响因子：
11.1
作者：
Geluk, A;Taneja, V;Ottenhoff, THM
通讯作者：
Ottenhoff, THM
DOI：
10.1126/science.1195568
发表时间：
2010-12-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lee YK;Mazmanian SK
通讯作者：
Mazmanian SK
影响因子：
4.4
作者：
Christensen, HR;Frokiær, H;Pestka, JJ
通讯作者：
Pestka, JJ
影响因子：
4.6
作者：
Kverka, M.;Zakostelska, Z.;Tlaskalova-Hogenova, H.
通讯作者：
Tlaskalova-Hogenova, H.
影响因子：
2.3
作者：
Greetham, HL;Gibson, GR;Collins, MD
通讯作者：
Collins, MD