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囊性纤维化患者肺部加重期气道真菌群-微生物群:一项培养与靶向测序研究

Airway Mycobiota-Microbiota During Pulmonary Exacerbation of Cystic Fibrosis Patients: A Culture and Targeted Sequencing Study.

作者信息

Angebault Cécile, Vandenborght Louise-Eva, Bassinet Laurence, Wizla Nathalie, Ferroni Agnès, Dessein Rodrigue, Remus Natacha, Thumerelle Caroline, Fauchet Nathalie, Epaud Ralph, Delhaes Laurence, Botterel Françoise

机构信息

Unité de Parasitologie-Mycologie, Département de Prévention, Diagnostic et Traitement Des Infections, CHU Henri Mondor, Assistance Publique Des Hôpitaux de Paris (APHP), Creteil, France.

UR Dynamyc 7380, Faculté de Santé, Univ Paris-Est Creteil (UPEC), Ecole Nationale Vétérinaire d'Alfort (ENVA); USC Anses, Maisons-Alfort, France, Creteil, France.

出版信息

Mycoses. 2025 Jan;68(1):e70024. doi: 10.1111/myc.70024.

Abstract

BACKGROUND

The airways of patients with cystic fibrosis (pwCF) harbour complex fungal and bacterial microbiota involved in pulmonary exacerbations (PEx) and requiring antimicrobial treatment. Descriptive studies analysing bacterial and fungal microbiota concomitantly are scarce, especially using both culture and high-throughput-sequencing (HTS).

OBJECTIVES

We analysed bacterial-fungal microbiota and inter-kingdom correlations in two French CF centres according to clinical parameters and antimicrobial choices.

METHODS

Forty-eight pwCF with PEx from Creteil (n = 24) and Lille (n = 24) CF centres were included over 2 years. Sputa were collected for culture and targeted-HTS (ITS2 and V3-V4 targets). Sequencing and culture data, along with clinical, radiological and treatment data, were analysed. Two-level stratified analysis was performed to study potential confounding factors (age, CF mutation, FEV1 and antibiotics) on the centre factor. Inter-kingdom correlations were analysed.

RESULTS

Significant differences in the bacterial microbiota profile were found between centres (p-value = 0.03). For mycobiota, the taxonomic distribution and diversity were comparable. HTS provided concordant but more detailed information than culture and increased detection of main CF fungi (> 25% more positive samples for Aspergillus or Scedosporium). FEV1 and systemic antibiotic before PEx influenced bacterial microbiota, but no clinical association was found with the mycobiota. No inter-kingdom correlation between Pseudomonas and fungi was found.

CONCLUSIONS

Describing concomitant bacterial and fungal communities of pwCF at the beginning of PEx using culture and HTS shows greater diversity in HTS and better detection in case of low microbial load. Interesting inter-kingdom correlations were observed, requiring further research on larger cohorts to understand the potential microbial interactions.

摘要

背景

囊性纤维化患者(pwCF)的气道中存在复杂的真菌和细菌微生物群,这些微生物群与肺部加重(PEx)有关,需要进行抗菌治疗。同时分析细菌和真菌微生物群的描述性研究很少,尤其是同时使用培养和高通量测序(HTS)的研究。

目的

我们根据临床参数和抗菌药物选择,分析了法国两个囊性纤维化中心的细菌-真菌微生物群及界间相关性。

方法

在两年时间里,纳入了来自克雷泰伊(n = 24)和里尔(n = 24)囊性纤维化中心的48例患有PEx的pwCF。收集痰液进行培养和靶向HTS(ITS2和V3-V4靶点)。对测序和培养数据以及临床、放射学和治疗数据进行分析。进行两级分层分析,以研究中心因素对潜在混杂因素(年龄、囊性纤维化突变、第一秒用力呼气容积和抗生素)的影响。分析界间相关性。

结果

各中心之间的细菌微生物群谱存在显著差异(p值 = 0.03)。对于真菌微生物群,分类分布和多样性具有可比性。HTS提供了与培养结果一致但更详细的信息,并且增加了对主要囊性纤维化真菌的检测(曲霉菌或赛多孢菌的阳性样本增加超过25%)。PEx前的第一秒用力呼气容积和全身使用抗生素会影响细菌微生物群,但未发现与真菌微生物群有临床关联。未发现铜绿假单胞菌与真菌之间的界间相关性。

结论

在PEx开始时使用培养和HTS描述pwCF的细菌和真菌群落,显示出HTS具有更大的多样性,并且在微生物负荷较低的情况下检测效果更好。观察到了有趣的界间相关性,需要对更大的队列进行进一步研究,以了解潜在的微生物相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ca/11736540/7b0f05157d75/MYC-68-e70024-g004.jpg

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