The microbiome in pediatric cystic fibrosis patients: the role of shared environment suggests a window of intervention.
The microbiome in pediatric cystic fibrosis patients: the role of shared environment suggests a window of intervention.
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DOI：
10.1186/2049-2618-2-14
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发表时间：
2014
期刊：
影响因子：
15.5
通讯作者：
O'Toole GA
中科院分区：
文献类型：
--
作者：
Hampton TH;Green DM;Cutting GR;Morrison HG;Sogin ML;Gifford AH;Stanton BA;O'Toole GA
囊性纤维化（CF）是由CFTR基因突变引起的，该基因易使气道感染。铜绿假单胞菌等病原体的慢性感染导致炎症，逐渐降低肺功能，导致发病和早期死亡。在之前对CF同卵双胞胎的研究中，我们证明了遗传修饰因子显著影响CF中持久性铜绿假单胞菌定植的建立。认识到铜绿假单胞菌以外的细菌对CF微生物组和相关病理也有贡献，我们对患有CF的儿科同卵双胞胎和非双胞胎兄弟姐妹的痰进行了深度测序，以表征儿科细菌群落及其遗传在其进化中的作用。我们发现，生活在一起的儿科患者的痰中微生物群落比分开生活的儿科患者的痰中微生物群落更相似，无论样本是来自同卵双胞胎还是来自生活在一起的非双胞胎CF兄弟姐妹，我们将其作为异卵双胞胎的代理。相比之下，成人群体相对单一，比儿科患者的微生物组多样性要少得多。综上所示，这些数据和其他近期研究表明，随着患者年龄的增长，CF微生物组的多样性降低，治疗变得更加难愈，并且以粘液样P. aeruginosa为主，并且与肺功能加速衰退有关。我们的研究表明，儿科患者的微生物组容易受到环境的影响，这表明保护年轻CF患者中发现的微生物群落结构的干预措施可能是可能的，也许可以减缓疾病的进展。
Cystic fibrosis (CF) is caused by mutations in the CFTR gene that predispose the airway to infection. Chronic infection by pathogens such as Pseudomonas aeruginosa leads to inflammation that gradually degrades lung function, resulting in morbidity and early mortality. In a previous study of CF monozygotic twins, we demonstrate that genetic modifiers significantly affect the establishment of persistent P. aeruginosa colonization in CF. Recognizing that bacteria other than P. aeruginosa contribute to the CF microbiome and associated pathology, we used deep sequencing of sputum from pediatric monozygotic twins and nontwin siblings with CF to characterize pediatric bacterial communities and the role that genetics plays in their evolution. We found that the microbial communities in sputum from pediatric patients living together were much more alike than those from pediatric individuals living apart, regardless of whether samples were taken from monozygous twins or from nontwin CF siblings living together, which we used as a proxy for dizygous twins. In contrast, adult communities were comparatively monolithic and much less diverse than the microbiome of pediatric patients. Taken together, these data and other recent studies suggest that as patients age, the CF microbiome becomes less diverse, more refractory to treatment and dominated by mucoid P. aeruginosa, as well as being associated with accelerated pulmonary decline. Our studies show that the microbiome of pediatric patients is susceptible to environmental influences, suggesting that interventions to preserve the community structure found in young CF patients might be possible, perhaps slowing disease progression.
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影响因子：
15.5
作者：
Price KE;Hampton TH;Gifford AH;Dolben EL;Hogan DA;Morrison HG;Sogin ML;O'Toole GA
通讯作者：
O'Toole GA
影响因子：
6.4
作者：
Madan JC;Koestler DC;Stanton BA;Davidson L;Moulton LA;Housman ML;Moore JH;Guill MF;Morrison HG;Sogin ML;Hampton TH;Karagas MR;Palumbo PE;Foster JA;Hibberd PL;O'Toole GA
通讯作者：
O'Toole GA
影响因子：
5.2
作者：
Gifford, Alex H.;Alexandru, Diana M.;O'Toole, George A.
通讯作者：
O'Toole, George A.
DOI：
10.1073/pnas.1120577109
发表时间：
2012-04-10
影响因子：
11.1
作者：
Zhao, Jiangchao;Schloss, Patrick D.;LiPuma, John J.
通讯作者：
LiPuma, John J.
影响因子：
5.1
作者：
Klepac-Ceraj, Vanja;Lemon, Katherine P.;Kolter, Roberto
通讯作者：
Kolter, Roberto