Nonhealing diabetic foot ulcers (DFUs) are a common and costly complication of diabetes. Microbial burden, or "bioburden," is believed to underlie delayed healing, although little is known of those clinical factors that may influence microbial load, diversity, and/or pathogenicity. We profiled the microbiomes of neuropathic nonischemic DFUs without clinical evidence of infection in 52 individuals using high-throughput sequencing of the bacterial 16S ribosomal RNA gene. Comparatively, wound cultures, the standard diagnostic in the clinic, vastly underrepresent microbial load, microbial diversity, and the presence of potential pathogens. DFU microbiomes were heterogeneous, even in our tightly restricted study population, but partitioned into three clusters distinguished primarily by dominant bacteria and diversity. Ulcer depth was associated with ulcer cluster, positively correlated with abundance of anaerobic bacteria, and negatively correlated with abundance of Staphylococcus. Ulcer duration was positively correlated with bacterial diversity, species richness, and relative abundance of Proteobacteria, but was negatively correlated with relative abundance of Staphylococcus. Finally, poor glycemic control was associated with ulcer cluster, with poorest median glycemic control concentrating to Staphylococcus-rich and Streptococcus-rich ulcer clusters. Analyses of microbial community membership and structure may provide the most useful metrics in prospective studies to delineate problematic bioburden from benign colonization that can then be used to drive clinical treatment.

译文

:非愈合性糖尿病足溃疡(DFU)是糖尿病的常见且代价高昂的并发症。尽管对影响微生物负荷,多样性和/或致病性的临床因素知之甚少,但是微生物负荷或“生物负荷”被认为是延迟愈合的基础。我们使用细菌16S核糖体RNA基因的高通量测序对52例无感染临床症状的神经性非缺血性DFU的微生物群进行了分析。相比之下,伤口培养物(临床上的标准诊断方法)在很大程度上代表了微生物负荷,微生物多样性以及潜在病原体的存在。即使在我们严格限制的研究人群中,DFU微生物群也是异质的,但被分为三类,主要以优势细菌和多样性为特征。溃疡深度与溃疡簇有关,与厌氧菌的数量呈正相关,与葡萄球菌的数量呈负相关。溃疡持续时间与细菌多样性,物种丰富度和变形杆菌相对丰度呈正相关,而与葡萄球菌相对丰度呈负相关。最后,血糖控制不佳与溃疡簇有关,最差的中位血糖控制集中于富含葡萄球菌和富含链球菌的溃疡簇。在前瞻性研究中,对微生物群落组成和结构的分析可能会提供最有用的指标,以从良性定殖中确定有问题的生物负荷,然后将其用于临床治疗。

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