Microbiomes of foot ulcers could predict clinical outcomes and responses to treatment


According to research led by the University of Wisconsin, the microbial communities associated with chronic wounds common in diabetic patients may predict whether those wounds heal or lead to amputations.

Lindsay Kalan, PhD, assistant professor of medical microbiology and immunology at the School of Medicine and Public Health at the University of Wisconsin-Madison led a study with colleagues, which analyzed data from 46 patients with neuropathic diabetic foot ulcers.

“We have evidence now that suggests we can use the microbiome to try and predict healing outcomes and use that to innovate for new therapies,” said Dr. Kalan in an article published on the university website. “That’s our ultimate goal — to try and shorten healing times and prevent amputation.”

Research showed that diabetic foot ulcers that never healed seemed to be exclusively infected with particular strains of Staphylococcus aureus, indicating these strains may delay healing.

Dr. Kalan’s team also found other common bacterial found in these wounds can impair or even improve healing. The study suggests that monitoring the microbiomes of diabetic foot ulcers could provide doctors with information on how to best treat these chronic and debilitating wounds.

Researchers collected the data from the ulcer microbiomes of the patients before their wounds were debrided. New microbial samples were taken every two weeks for 26 weeks while tracking the outcome of the ulcers.

The bacterium S. aureus, known for its resistance to antibiotics, was found in a majority of the wounds. However, the presence of S. aureus did not predict whether a wound would heal or not. With high-resolution data on individual strains of S. aureus, researchers learned that some strains only resided in wounds that did not heal during the study.

“When we looked at the genome of these strains, we found that they were enriched in virulence factors like enterotoxins and that they had more antibiotic resistance genes, so they were better equipped to cause a more invasive infection compared to some of the other strains we detected,” said Dr. Kalan.

Researchers continued sampling the microbiomes of ulcers throughout the study and were able to see the microbial community changed in response to treatment. As expected, the team found little change in the ulcer microbiome of patients treated.

On the other hand, debridement reduced the diversity of bacteria colonizing the wounds in ulcers that went on to heal. The results suggest that the disrupted microbial community could serve as a sign of successful debridement, helping inform the course of treatment.

“If we can use the microbial community to tell within 24 hours that debridement wasn’t effective and a patient needs to come back for more treatment, it would greatly reduce care time and the patient’s time away from work,” Dr. Kalan continued.

In an effort to better understand how the microbiomes might directly affect wound healing, the researchers created microbial communities in a mouse model of diabetic ulcers by transferring human bacterial strains to ulcers in mice and monitored how the wounds healed.

The strains of S. aureus found in non-healing ulcers delayed healing by several weeks, further implicating these particular strains in creating worse clinical outcomes.

Another common member of wound microbiomes, Alcaligenes faecalis, was found to reduce the growth of ulcers in the mouse model and wounds infected with these bacteria healed nearly as quickly as uninfected wounds.

According to Dr. Kalan, the relatively benign impact A. faecalis had on wounds may be because it stimulates beneficial inflammation in the wounded skin, indicating that some community members could even offset the detrimental effects of more harmful bacteria.

#Footulcers #microbiomes #ulcers

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