Strain- and Species-Level Variation in the Microbiome of Diabetic Wounds Is Associated with Clinical Outcomes and Therapeutic Efficacy
Strain- and Species-Level Variation in the Microbiome of Diabetic Wounds Is Associated with Clinical Outcomes and Therapeutic Efficacy
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DOI：
10.1016/j.chom.2019.03.006
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发表时间：
2019-05-08
影响因子：
30.3
通讯作者：
Grice, Elizabeth A.
中科院分区：
文献类型：
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作者：
Kalan, Lindsay R.;Meise, Jacquelyn S.;Grice, Elizabeth A.
慢性伤口是糖尿病的主要并发症，与高发病率和医疗保健费用有关。为了研究定植微生物群在糖尿病创面愈合、临床结果和干预反应中的作用，我们对神经病理性糖尿病足溃疡(DFU)患者进行了一项前瞻性纵向研究。后基因组鸟枪测序显示，金黄色葡萄球菌菌株水平的变异和生物膜形成的遗传特征与不良结局相关。金黄色葡萄球菌的培养伤口分离株在小鼠模型中产生了与患者预后相对应的不同表型，而通常被认为是共生或污染物的伤口“旁观者”，如纹状棒杆菌和粪产碱杆菌，也显著影响了伤口的严重程度和愈合。抗生素耐药基因广泛存在，清创而不是抗生素治疗显著改变了患者的DFU微生物区系，结果更有利。这些发现表明，DFU微生物区系可能是临床结果和治疗干预反应的标志。
Chronic wounds are a major complication of diabetes associated with high morbidity and health care expenditures. To investigate the role of colonizing microbiota in diabetic wound healing, clinical outcomes, and response to interventions, we conducted a longitudinal, prospective study of patients with neuropathic diabetic foot ulcers (DFU). Metagenomic shotgun sequencing revealed that strain-level variation of Staphylococcus aureus and genetic signatures of biofilm formation were associated with poor outcomes. Cultured wound isolates of S. aureus elicited differential phenotypes in mouse models that corresponded with patient outcomes, while wound "bystanders'' such as Corynebacterium striatum and Alcaligenes faecalis, typically considered commensals or contaminants, also significantly impacted wound severity and healing. Antibiotic resistance genes were widespread, and debridement, rather than antibiotic treatment, significantly shifted the DFU microbiota in patients with more favorable outcomes. These findings suggest that the DFU microbiota may be a marker for clinical outcomes and response to therapeutic interventions.