The Neuropathic Diabetic Foot Ulcer Microbiome Is Associated With Clinical Factors
Open accessAbstract
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.
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Polymicrobial presence (bioburden) is well documented in chronic wounds and can play a major role in impaired wound healing even without clinical signs of infection.
“Polymicrobial presence (bioburden) has been well documented in chronic wounds and can play a major role in impaired wound healing, even in the absence of clinical signs of infection (Fig. 3) (163, 165).”
From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [165]
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- Authors
- Gardner, S. E., Hillis, S. L., Heilmann, K., Segre, J. A., & Grice, E. A.
- Affiliations
- University of Iowa (US)
- National Institutes of Health (US)
- University of Pennsylvania (US)
- Corresponding author
- Gardner, Sue E.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2013-02-14
- Volume
- 62
- Issue
- 3
- Pages
- 923-930
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3581190
- OpenAlex
- W2131452956
- Cited by
- 320
- References
- 40
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 25 · 2023: 29 · 2022: 35 · 2021: 34 · 2020: 26 · 2019: 21 · 2018: 24 · 2017: 30 · 2016: 22 · 2015: 12 · 2014: 24 · 2013: 9 · 2012: 1
- FWCI
- 11.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Iowa Research Online (The University of Iowa) (submittedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health
- National Institute of Nursing Research (R01NR009448, NR009448)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R00AR060873)
- National Center for Research Resources (UL1RR024979)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Microbiology › Actinomycetales infections and treatment
- Keywords
- diabetic foot ulcer, neuropathic diabetic foot, wound microbiota, microbial load, bacterial diversity, Staphylococcus, Streptococcus, anaerobic bacteria, Proteobacteria, glycemic control, ulcer depth, ulcer duration, 16S rRNA gene sequencing
- MeSH terms
- Adult, Aged, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, RNA, Bacterial, RNA, Ribosomal, 16S, Severity of Illness Index, Staphylococcal Infections, Staphylococcus, Streptococcal Infections, Streptococcus, United States, Wound Healing, Prevalence, Diabetic Foot, Proteobacteria
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