Longitudinal shift in diabetic wound microbiota correlates with prolonged skin defense response

Abstract

Diabetics frequently suffer from chronic, nonhealing wounds. Although bacterial colonization and/or infection are generally acknowledged to negatively impact wound healing, the precise relationship between the microbial community and impaired wound healing remains unclear. Because the host cutaneous defense response is proposed to play a key role in modulating microbial colonization, we longitudinally examined the diabetic wound microbiome in tandem with host tissue gene expression. By sequencing 16S ribosomal RNA genes, we show that a longitudinal selective shift in wound microbiota coincides with impaired healing in diabetic mice ( Lepr db/db ; db/db). We demonstrate a parallel shift in longitudinal gene expression that occurs in a cluster of genes related to the immune response. Further, we establish a correlation between relative abundance of Staphylococcus spp. and the expression of cutaneous defense response genes. Our data demonstrate that integrating two types of global datasets lends a better understanding to the dynamics governing host–microbe interactions.

Aerobic bacterial microbiota of the conjunctiva in diabetic patients with normal and altered glycated hemoglobin levels in two regions in Brazil

“…The presence of pathogenic microorganisms in the conjunctival microbiota of patients without any evident clinical infection, as observed in the present study, which is associated with the presence of immunological alterations described in this group of individuals, could have the effect of increasing the risk of developing infection following intraocular procedures (20) . When performing an assessment according to age group, a greater number of diabetic and non-diabetic patients were found between 61 and 70 years of age and older than 70 years of age, regardless of glycemic control (patients with controlled and non-controlled diabetes) in the two regions studied, although the difference was not statistically significant.…”

Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

“…In addition to the collagens that were altered in the diabetic rat skin, other transcriptome study in normal and diabetic db/db mice skin, transcripts upregulated during diabetes were overrepresented in categories of lipid metabolism and wounding, whereas the downregulated genes majorly mapped onto developmental processes (29). .…”

“…Data were analyzed with the 2 -ΔΔCt method, where the average Ct (ΔCt) is the normalized Ct values of the miRNA with that of U87 (reference control) and miRNAs altered in (a) unwounded diabetic rat skin compared with normal rat skin and (b) diabetic skin wound compared with normal skin wound in rats (d 7 postwounding), with a p value <0.05 (compared with the in the prolonged inflammatory stage versus the normal wound that undergoes an orchestrated normal healing process. As described by Grice et al (29), before attempting to evaluate the altered miRNA signature in the rat wounded tissue during diabetes, we first compared the status of miRNAs in normal and diabetic rat unwounded skin using the Taqman Array Rodent miRNA card (Applied Biosystems) to set a baseline for alterations as a result of wounding. As compared with the normal rat skin, 10 miRNAs were differentially expressed in the skin of diabetic rats; two were upregulated and eight were downregulated ( Figure 2A).…”

Traumatic Wound Microbiome Workshop

“…Grice, of the National Human Genome Research Institute, presented her insights into the interaction between cutaneous tissue and the microbiome of traumatic and chronic wounds, derived from animal studies on traumatic and diabetic wounds in a mouse model [6]. During the presentation, she eschewed culture results entirely after an initial slide demonstrating that culture did not capture the diversity of the skin flora.…”