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在一项基于大规模人群的研究中确定对哮喘有保护作用的真菌候选物。

Identification of fungal candidates for asthma protection in a large population-based study.

作者信息

Mueller-Rompa Susanne, Janke Tobias, Schwaiger Karin, Mayer Melanie, Bauer Johann, Genuneit Jon, Braun-Fahrlaender Charlotte, Horak Elisabeth, Boznanski Andrzej, von Mutius Erika, Ege Markus J

机构信息

Dr von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany.

Chair of Animal Hygiene, Technische Universität München, Munich, Germany.

出版信息

Pediatr Allergy Immunol. 2017 Feb;28(1):72-78. doi: 10.1111/pai.12665. Epub 2016 Nov 3.

Abstract

BACKGROUND

Exposure to molds has been related to asthma risk both positively and negatively, depending on the environmental setting. The pertinent results are based on generic markers or culturing methods although the majority of present fungi cannot be cultured under laboratory conditions. The aim of the present analysis was to assess environmental dust samples for asthma-protective fungal candidates with a comprehensive molecular technique covering also non-cultivable and non-viable fungi.

METHODS

Mattress dust samples of 844 children from the GABRIELA study were analyzed by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) of the fungus-specific internal transcribed spacer (ITS) region. Known asthma candidate species were tested for their associations with asthma, and further gel positions were sought to explain the above. As a second, data-driven, analysis, we tested the association of each individual gel position with asthma.

RESULTS

In the hypothesis-driven approach, Penicillium chrysogenum emerged with an odds ratio of 0.80 (95% confidence interval 0.66-0.96; p = 0.020). The effect size was changed by 39% toward the null when adjusting for the two bands 683 (DNA of Metschnikowia sp., Aureobasidium spp.) and 978 (DNA of Epicoccum spp., Galactomyces spp., uncultured Penicillium). The data-driven approach yielded an additional band (containing DNA of Pseudotaeniolina globosa) with reduced risk of asthma (OR = 0.80 [0.66-0.96], p = 0.012).

CONCLUSIONS

A large population-based study revealed several fungal taxa with inverse associations with childhood asthma. Molds produce a variety of bioactive compounds with detrimental but also beneficial immunoregulatory capacities, which renders them promising targets for further asthma research.

摘要

背景

接触霉菌与哮喘风险的关系呈正向或负向,这取决于环境状况。尽管目前大多数真菌无法在实验室条件下培养,但相关结果是基于通用标记或培养方法得出的。本分析的目的是采用一种全面的分子技术评估环境灰尘样本中是否存在具有哮喘保护作用的真菌候选物,该技术还涵盖了不可培养和无活力的真菌。

方法

对来自加布里埃拉研究的844名儿童的床垫灰尘样本进行真菌特异性内转录间隔区(ITS)区域的聚合酶链反应-单链构象多态性(PCR-SSCP)分析。检测已知的哮喘候选菌种与哮喘的关联,并寻找其他凝胶条带位置来解释上述情况。作为第二项数据驱动分析,我们检测了每个单独凝胶条带位置与哮喘的关联。

结果

在假设驱动的方法中,产黄青霉出现的比值比为0.80(95%置信区间0.66-0.96;p = 0.020)。在对683(梅奇尼科夫酵母属、 Aureobasidium spp.的DNA)和978(附球菌属、半乳糖酵母属、未培养青霉的DNA)这两条带进行校正后,效应大小向无效方向改变了39%。数据驱动的方法产生了另一条带(包含球形假带孢酵母的DNA),其哮喘风险降低(OR = 0.80 [0.66-0.96],p = 0.012)。

结论

一项基于大量人群的研究揭示了几种与儿童哮喘呈负相关的真菌类群。霉菌产生多种具有有害但也有益的免疫调节能力的生物活性化合物,这使其成为进一步哮喘研究的有前景的靶点。

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