Journal Article

The Neuropathic Diabetic Foot Ulcer Microbiome Is Associated With Clinical Factors

Hillis, Stephen L., Heilmann, Kris, Gardner, Sue E., Segre, Julia A., Grice, Elizabeth A.

2013

Overview

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.

• Publisher: American Diabetes Association
• Subject: Adult / Aged / Analysis / Antibiotics / Associated diseases and complications / Bacteria / Biological and medical sciences / Complications / Cross-Sectional Studies / Diabetes / Diabetes. Impaired glucose tolerance / Diabetic foot / Diabetic Foot - complications / Diabetic Foot - microbiology / Diabetic Foot - physiopathology / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Female / Foot diseases / Humans / Infections / Leg ulcers / Male / Medical sciences / Microbiota / Microorganisms / Middle Aged / Pathogens / Patient outcomes / Prevalence / Proteobacteria - classification / Proteobacteria - isolation & purification / Proteobacteria - metabolism / Proteobacteria - pathogenicity / Review boards / RNA, Bacterial - metabolism / RNA, Ribosomal, 16S - metabolism / Severity of Illness Index / Staphylococcal Infections - complications / Staphylococcal Infections - epidemiology / Staphylococcal Infections - microbiology / Staphylococcus - classification / Staphylococcus - isolation & purification / Staphylococcus - metabolism / Staphylococcus - pathogenicity / Streptococcal Infections - complications / Streptococcal Infections - epidemiology / Streptococcal Infections - microbiology / Streptococcus - classification / Streptococcus - isolation & purification / Streptococcus - metabolism / Streptococcus - pathogenicity / United States - epidemiology / Wound Healing