Abstract Detail

Exploring the environmental side of the disease triangle in animal pathogens

Hodkinson, Brendan P. [1], Gardner, Sue E. [2], Tyldsley, Amanda S. [1], Boudhar, Sanaa [3], Margolis, David J. [1], Grice, Elizabeth A. [1].

The diabetic foot ulcer microbiome: association with clinical factors and outcomes.

Diabetes affects nearly 19 million individuals in the United States. Among these, 3 million will develop at least one diabetic foot ulcer (DFU). DFUs are associated with poor quality of life, increased mortality and result in 65,000 lower limb amputations annually. Although microbial colonization and infection are believed to significantly impair DFU healing and lead to ulcer-related complications, little solid evidence exists linking microbial exposures to the failure of a foot ulcer to heal. Furthermore, little is known of those clinical factors that may influence the wound environment and thus various dimensions of the colonizing microbiota. The overall purpose of our study is to characterize the dynamic DFU microbiome in relation to outcomes and clinical factors. The fungal component of the DFU microbiome is of special interest as persistent high blood glucose may encourage fungal growth, potentially leading to fungi-related complications and impaired healing. However, fungal cultures are typically slow growing and are not included as part of standard of care cultures. Furthermore, no chronic wounds have ever been investigated using fungal ITS sequencing. We longitudinally profiled the microbiota colonizing neuropathic, non-ischemic DFUs of 100 patients at 2-week intervals from time of presentation to healing by deep sequencing of the fungal ITS region (in parallel with the bacterial 16S rRNA gene). All subjects received standardized treatment, which did not include systemic or topical antibiotics. Samples were collected using Levine’s swab technique, which samples fluid from the deep tissue layers. Clinical factors measured at each visit included: blood glucose, ulcer size and depth, extent of necrotic tissues, and complete blood count. Approximately 80% of samples showed detectable products after PCR amplification with standard fungal ITS primers. Preliminary deep sequencing analyses of a subset of samples revealed that certain DFU-associated fungal communities are dominated by either Candida or Saccharomyces, although not all wounds have a clearly dominant fungal group. We are further analyzing the stability of DFU microbiota and how dynamics may be associated with clinical factors and outcomes as data become available. Our long-term goal is to delineate the role of bioburden (fungal and bacterial) in impaired healing of DFUs, and to identify microbiome-related biomarkers that could help guide DFU management.

Related Links:
Grice Lab website

1 - University of Pennsylvania, Department of Dermatology, Perelman School of Medicine, 421 Curie Blvd., BRB 10th Floor, Philadelphia, PA, 19104, USA
2 - University of Iowa, College of Nursing, 50 Newton Road, 320 CNB, Iowa City, Iowa, 52242, USA
3 - University of Pennsylvania, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, 423 Guardian Drive, Blockley Hall 6th Floor, Philadelphia, PA, 19104, USA

Keywords:
medical
disease
community structure
Illumina
biomarkers.

Presentation Type: Symposium or Colloquium Presentation
Session: SY2
Location: Room 103 AB/Kellogg Hotel and Conference Center
Date: Monday, June 9th, 2014
Time: 4:00 PM
Number: SY2003
Abstract ID:82
Candidate for Awards:None