Temporal Stability in Chronic Wound Microbiota Is Associated With Poor Healing

Abstract

Microbial burden of chronic wounds is believed to play an important role in impaired healing and development of infection-related complications. However, clinical cultures have little predictive value of wound outcomes, and culture-independent studies have been limited by cross-sectional design and small cohort size. We systematically evaluated the temporal dynamics of the microbiota colonizing diabetic foot ulcers (DFU), a common and costly complication of diabetes, and its association with healing and clinical complications. Dirichlet multinomial mixture modeling, Markov chain analysis, and mixed-effect models were used to investigate shifts in the microbiota over time and its associations with healing. Here we show to our knowledge previously unreported temporal dynamics of the chronic wound microbiome. Microbiota community instability was associated with faster healing and improved outcomes. DFU microbiota were found to exist in one of four community types that experienced frequent and non-random transitions. Transition patterns and frequencies associated with healing time. Exposure to systemic antibiotics destabilized the wound microbiota, rather than altering overall diversity or relative abundance of specific taxa. This study provides to our knowledge previously unreported evidence that the dynamic wound microbiome is indicative of clinical outcomes and may be a valuable guide for personalized management and treatment of chronic wounds.

Skin microbiota–host interactions

“…For example, an S. epidermidis cell wall component mitigates inflammation by binding to TLR2, limiting tissue damage and promoting wound healing 63 . Other commensal microbiota are also likely to contribute to wound healing, which is a dynamic process associated with global shifts in the skin microbiome; wound bed microbiomes that fail to shift are associated with chronic ulcers 64,65 . Within chronic wounds, fungi and bacteria form mixed biofilms and certain fungal taxa, such as the phylum Ascomycota , are predictive of wounds that take more than eight weeks to heal.…”

A systematic literature review of the human skin microbiome as biomarker for dermatological drug development

“…The role of the skin microbiome in UC was explored in 10 different studies, Table 1 37, 38, 39, 40, 41, 42, 43, 44, 45, 46. Current research into UC microbiome, comprises larger, longitudinal studies, compared to those in PV and HS.…”

“…The skin mycobiota of diabetic foot ulcers was longitudinally assessed and was observed to be highly heterogeneous over time and between subjects while the diversity increased upon antibiotic treatment 45. There have been similar efforts to reveal correlations between patient metadata, treatment and/or clinical outcomes and the cutaneous microbiome in studies investigating the microbiota in UC 38, 42, 43, 44, 46. Overall, the most common found genus in these studies was Staphylococcus , with Staphylococcus aureus the most common species.…”

“…For UC inconsistencies in study design, sampling methods and the heterogeneity of the disease group also limit the comparability of study findings. There appears to be a relationship between certain species, types of ulcers and ulcer duration 42, 46. However, longitudinal studies with frequent standard sampling and standard analysis procedures are necessary to make a recommendation.…”

Pathogenesis of wound healing disorders in the elderly

“…Furthermore, fungal diversity seems to have a predictive value with respect to the duration of the healing process. In this context, mixed fungal/bacterial biofi lms are associated with a poor prognosis [ 39,40 ] .…”