Redefining the Chronic-Wound Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing.
Redefining the Chronic-Wound Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing.
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DOI：
10.1128/mbio.01058-16
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发表时间：
2016-09-06
期刊：
影响因子：
6.4
通讯作者：
Grice EA
中科院分区：
文献类型：
--
作者：
Kalan L;Loesche M;Hodkinson BP;Heilmann K;Ruthel G;Gardner SE;Grice EA
慢性不愈合伤口被认为是一种无声的流行病，导致显著的发病率和死亡率，特别是在老年人、糖尿病患者和肥胖人群中。假设伤口床中的多微生物生物膜破坏了皮肤愈合的高度协调和顺序事件。对慢性伤口微生物组的培养依赖性和非依赖性研究几乎完全集中在细菌上，忽略了我们假设的真菌对愈合受损和并发症发展的重要贡献。在这里，我们首次表明慢性伤口中的真菌群落（真菌生物群）可预测愈合时间，与不良结局相关，并形成混合的真菌-细菌生物膜。我们纵向分析了100例未愈合的糖尿病足溃疡，并对泛真菌内转录间隔区1（ITS 1）位点进行了高通量测序，估计高达80%的伤口含有真菌，而平行培养仅捕获了5%的定植伤口。随着时间的推移和受试者之间的“真菌生物群”是高度异质性的。真菌多样性随着抗生素的使用和临床并发症的发生而增加。在研究开始时，在愈合时间>8周的伤口中，子囊菌门的比例显著更大（P = 0.015）。伤口坏死与致病性真菌物种明显相关，而被鉴定为过敏性丝状真菌的分类群与低水平的全身炎症相关。定向培养的伤口稳定定植的病原体显示，界间生物膜之间形成酵母菌和coisolated细菌。结合起来，我们的分析提供了伤口愈合受损期间真菌生物群系的增强分辨率，其在慢性疾病中的作用以及对临床结局的影响。对于多种疾病来说，伤口是一种被低估但严重的并发症。高风险人群，如糖尿病患者，一生中有25%的风险会发展成慢性伤口。大多数与慢性伤口相关的微生物组研究都集中在细菌上，但真菌与临床结局的关系仍有待阐明。在这里，我们描述了100例糖尿病足溃疡患者的动态真菌群落。我们发现，随着时间的推移，社区是不稳定的，但在第一次临床表现，不同门的相对比例预测愈合时间。未通过培养鉴定的病原性真菌存在于坏死伤口中，并且与不良预后相关。在真菌稳定定殖的伤口中，我们鉴定了能够与细菌一起形成生物膜的酵母。我们的研究结果阐明了真菌菌群与伤口预后和愈合的关系。
Chronic nonhealing wounds have been heralded as a silent epidemic, causing significant morbidity and mortality especially in elderly, diabetic, and obese populations. Polymicrobial biofilms in the wound bed are hypothesized to disrupt the highly coordinated and sequential events of cutaneous healing. Both culture-dependent and -independent studies of the chronic-wound microbiome have almost exclusively focused on bacteria, omitting what we hypothesize are important fungal contributions to impaired healing and the development of complications. Here we show for the first time that fungal communities (the mycobiome) in chronic wounds are predictive of healing time, associated with poor outcomes, and form mixed fungal-bacterial biofilms. We longitudinally profiled 100, nonhealing diabetic-foot ulcers with high-throughput sequencing of the pan-fungal internal transcribed spacer 1 (ITS1) locus, estimating that up to 80% of wounds contain fungi, whereas cultures performed in parallel captured only 5% of colonized wounds. The “mycobiome” was highly heterogeneous over time and between subjects. Fungal diversity increased with antibiotic administration and onset of a clinical complication. The proportions of the phylum Ascomycota were significantly greater (P = 0.015) at the beginning of the study in wounds that took >8 weeks to heal. Wound necrosis was distinctly associated with pathogenic fungal species, while taxa identified as allergenic filamentous fungi were associated with low levels of systemic inflammation. Directed culturing of wounds stably colonized by pathogens revealed that interkingdom biofilms formed between yeasts and coisolated bacteria. Combined, our analyses provide enhanced resolution of the mycobiome during impaired wound healing, its role in chronic disease, and impact on clinical outcomes. Wounds are an underappreciated but serious complication for a diverse spectrum of diseases. High-risk groups, such as persons with diabetes, have a 25% lifetime risk of developing a wound that can become chronic. The majority of microbiome research related to chronic wounds is focused on bacteria, but the association of fungi with clinical outcomes remains to be elucidated. Here we describe the dynamic fungal communities in 100 diabetic patients with foot ulcers. We found that communities are unstable over time, but at the first clinical presentation, the relative proportions of different phyla predict healing times. Pathogenic fungi not identified by culture reside in necrotic wounds and are associated with a poor prognosis. In wounds stably colonized by fungi, we identified yeasts capable of forming biofilms in concert with bacteria. Our findings illuminate the associations of the fungal mycobiome with wound prognosis and healing.