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

无法愈合的糖尿病足溃疡 (DFUs) 是糖尿病的常见且昂贵的并发症。微生物负担或 “生物负荷” 被认为是延迟愈合的基础,尽管对可能影响微生物负荷,多样性和/或致病性的那些临床因素知之甚少。我们使用细菌16s核糖体RNA基因的高通量测序,对52例个体的神经性非缺血性DFUs的微生物群进行了分析,而没有感染的临床证据。相比之下,伤口培养物 (临床上的标准诊断) 大大低估了微生物负荷,微生物多样性和潜在病原体的存在。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,但分为三个簇,主要由优势细菌和多样性区分。溃疡深度与溃疡簇有关,与厌氧菌的丰度呈正相关,与葡萄球菌的丰度呈负相关。溃疡持续时间与细菌多样性,物种丰富度和变形菌的相对丰度呈正相关,但与葡萄球菌的相对丰度呈负相关。最后,血糖控制不佳与溃疡群有关,中位血糖控制最差的集中于富含葡萄球菌和富链球菌的溃疡群。微生物群落成员和结构的分析可能会在前瞻性研究中提供最有用的指标,以从良性定植中描绘出有问题的生物负荷,然后将其用于推动临床治疗。

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