The role of the microbiome in nonhealing diabetic wounds

Abstract

Wound healing is a highly coordinated and complex process, and there can be devastating consequences if it is interrupted. It is believed that, in combination with host factors, microorganisms in a wound bed can not only impair wound healing but can lead to stalled, chronic wounds. It is hypothesized that the wound microbiota persists in chronic wounds as a biofilm, recalcitrant to antibiotic and mechanical intervention. Cultivation-based methods are the gold standard for identification of pathogens residing in wounds. However, these methods are biased against fastidious organisms, and do not capture the full extent of microbial diversity in chronic wounds. Thus, the link between specific microbes and impaired healing remains tenuous. This is partially because local infection and, more specifically, the formation of a biofilm, is difficult to diagnose. This has led to research efforts aimed at understanding if biofilm formation delays healing and leads to persistent and chronic infection. Circumventing challenges associated with culture-based estimations, advances in high-throughput sequencing analysis has revealed that chronic wounds are host to complex, diverse microbiomes comprising multiple species of bacteria and fungi. Here, we discuss how the use of genomic methodologies to study wound microbiomes has advanced the current understanding of infection and biofilm formation in chronic wounds.

Bacteriophages for Chronic Wound Treatment: From Traditional to Novel Delivery Systems

“…Microbial flora in chronic wounds appears to be complex and changes over time [2,39]. Aerobic or facultative pathogens (e.g., Staphylococcus aureus, Pseudomonas aeruginosa, and beta-hemolytic streptococci) are particularly prevalent in infections and delay wound healing [2,18,31,40]. In diabetic foot ulcers, S. aureus is the prevalent isolate together with others such as P. aeruginosa, Enterococcus spp., Escherichia coli, Enterobacter spp., Proteus mirabilis, and Klebsiella pneumonia [41][42][43].…”

“…In diabetic foot ulcers, S. aureus is the prevalent isolate together with others such as P. aeruginosa, Enterococcus spp., Escherichia coli, Enterobacter spp., Proteus mirabilis, and Klebsiella pneumonia [41][42][43]. In burn wounds, the presence of pathogens such as P. aeruginosa together with K. pneumonia, Stenotrophomonas maltophilia, and Enterobacteriaceae spp., and all multidrug-resistant (MDR) or even totally drug-resistant organisms can be deadly [18]. The leading cause of death of those burn injury patients who survive longer than 72 h is reported to be a microbial infection, causing 43% to 65% of mortality (reviewed in [44]).…”

The beneficial effect of traditional Japanese herbal (Kampo) medicine, Hochu‐ekki‐to (Bu‐Zhong‐Yi‐Qi‐Tang), for patients with chronic wounds refractory to conventional therapies: A prospective, randomized trial

“…The causes of chronic skin wounds include a complex combination of local and systemic factors, such as circulatory dysfunction, infection, wound duration, malnutrition, endocrine‐metabolic disturbances, aging, and immunodeficiency . Although multidisciplinary treatments are necessary for chronic wounds and various methods of treatment have been employed for years, some cases remain refractory to existing treatments, and the wound healing processes do not progress for unclear reasons …”

“…To date, there has been no clinical study on the relationship between HET and wound healing. We hypothesized that HET as an adjunctive therapy would be useful for promoting the healing of chronic wounds, as wounds are microecological environments filled with large amounts of diverse and often virulent microbes . The impact of HET on patients with chronic wounds in which the progression of wound healing had been prolonged for >3 weeks was investigated in a prospective, randomized trial.…”

“…The causes of chronic skin wounds include a complex combination of local and systemic factors, such as circulatory dysfunction, infection, wound duration, malnutrition, endocrine-metabolic disturbances, aging, and immunodeficiency. [1][2][3][4] Although multidisciplinary treatments are necessary for chronic wounds and various methods of treatment have been employed for years, some cases remain refractory to existing treatments, and the wound healing processes do not progress for unclear reasons. [5][6][7][8][9] Hochu-ekki-to (HET; Bu-Zhong-Yi-Qi-Tang in Chinese) is a traditional Japanese herbal medicine that originated in China and is commonly used to treat severe weakness, loss of appetite, and indigestion in elderly patients and to prevent opportunistic infections in infection-prone patients.…”