Genome-wide mapping of gene-microbiota interactions in susceptibility to autoimmune skin blistering.
Genome-wide mapping of gene-microbiota interactions in susceptibility to autoimmune skin blistering.
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DOI：
10.1038/ncomms3462
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发表时间：
2013
影响因子：
16.6
通讯作者：
Ibrahim SM
中科院分区：
文献类型：
--
作者：
Srinivas G;Möller S;Wang J;Künzel S;Zillikens D;Baines JF;Ibrahim SM
慢性炎症性疾病的易感性由免疫遗传和环境风险因素决定。居民微生物群落通常在健康和患病状态之间存在差异，但这些差异是否具有主要病因学重要性或继发于改变的炎症环境仍然在很大程度上未知。在此，我们提供了宿主基因-微生物群相互作用导致获得性大疱性表皮病（一种自身抗体诱导的炎症性皮肤病）小鼠模型中疾病风险的证据。使用先进的杂交，我们确定了导致皮肤微生物群变异性、皮肤起泡易感性及其重叠的遗传位点。此外，通过将细菌物种丰度作为疾病的协变量，我们揭示了一种新的疾病位点。大多数已确定的协变量分类群的特征在于丰度降低与疾病风险增加相关，这提供了在预防疾病中发挥主要作用的证据。这些推定的益生菌物种或物种组合的进一步表征为预防性和治疗性治疗开发提供了有希望的潜力。 影响皮肤的炎性疾病的发病机制是多因素的。Srinivas等人表明，皮肤微生物群的多样性是决定获得性大疱性表皮病（一种慢性皮肤粘膜自身免疫性皮肤起泡疾病）易感性的关键因素。
Susceptibility to chronic inflammatory diseases is determined by immunogenetic and environmental risk factors. Resident microbial communities often differ between healthy and diseased states, but whether these differences are of primary aetiological importance or secondary to the altered inflammatory environment remains largely unknown. Here we provide evidence for host gene–microbiota interactions contributing to disease risk in a mouse model of epidermolysis bullosa acquisita, an autoantibody-induced inflammatory skin disease. Using an advanced intercross, we identify genetic loci contributing to skin microbiota variability, susceptibility to skin blistering and their overlap. Furthermore, by treating bacterial species abundances as covariates with disease we reveal a novel disease locus. The majority of the identified covariate taxa are characterized by reduced abundance being associated with increased disease risk, providing evidence of a primary role in protection from disease. Further characterization of these putative probiotic species or species assemblages offers promising potential for preventative and therapeutic treatment development. The pathogenesis of inflammatory disorders afflicting the skin is multifactorial. Srinivas et al. show that diversity of the skin microbiota is a critical factor determining the susceptibility to epidermolysis bullosa acquisita, a chronic mucocutaneous autoimmune skin blistering disease.
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DOI：
10.1111/j.1087-0024.2004.00833.x
发表时间：
2004-01-01
影响因子：
--
作者：
Aoki, V;Millikan, RC;Diaz, LA
通讯作者：
Diaz, LA
DOI：
10.1073/pnas.0807920105
发表时间：
2008-11-18
影响因子：
11.1
作者：
Fierer, Noah;Hamady, Micah;Knight, Rob
通讯作者：
Knight, Rob
影响因子：
6.5
作者：
Ludwig, Ralf J.;Mueller, Susen;Ibrahim, Saleh M.
通讯作者：
Ibrahim, Saleh M.
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
作者：
Asghari, Farahnaz;Fitzner, Brit;Jaster, Robert
通讯作者：
Jaster, Robert