Skin bacteria different in diabetic mice

HONOLULU – Too much of the wrong type of skin bacteria may keep diabetics from healing, new research suggests.

People with diabetes have a notoriously hard time healing from skin wounds. New research on diabetic mice suggests that bacteria normally present on healthy skin may play a role in wound healing, says Elizabeth Grice, a researcher at the National Human Genome Research Institute in Bethesda, Md. Grice presented results of a study comparing bacterial diversity on the skin of diabetic and normal mice October 23 during the annual meeting of the American Society of Human Genetics.

The work aims to find out how bacteria and other microorganisms on the skin — known collectively as the skin microbiome — affect health.

Grice and her colleagues had recently completed a survey of bacteria populating the skin of healthy people and found a wealth of diversity from individual to individual and from body part to body part.

At any given time, about 15 percent of diabetes patients will have a slow-healing wound, Grice says. Previous laboratory work to grow bacteria from cultures of diabetic wounds revealed that the wounds contain Staphylococcus, Streptococcus, Pseudomonas, Enterococcus and Corynebacterium. But Grice’s survey of healthy skin also found that those bacteria are a normal part of the healthy skin microbiome.

In order to find out how the microbes in the wounds of diabetic mice differ from those in the wounds of healthy animals, Grice compared bacteria from the skin of diabetic mice with those from the skin of the mice’s healthy siblings. The researchers first shaved the backs of both types of mice and found that the diabetic mice have inflamed, fragile skin. Sequencing DNA from swabs taken from the mice showed that diabetic mice have 40 times more bacteria on their skin than healthy mice, but fewer types of microbes.

The researchers then used a skin punch, like those used by dermatologists to take a skin sample, to make a small wound on the mice’s backs. As the wounds healed, the team collected bacteria and skin samples to find out how the population of bacteria and the mice’s response to the wound changed over time.

Wounds in normal mice healed in about two weeks, but healing took nearly a month for the wounds on diabetic mice. Even after the wounds healed, the skin around the wound site was inflamed in the diabetic mice, but not in the normal mice, the researchers found.

The diabetic mice had higher levels of Staphylococcus and other rod-shaped bacteria, such as Aerococcus and Weissella, in their wounds, the team discovered. The injury sites in normal mice had increased levels of Clostridium and Streptococcus bacteria. These types of bacteria may occupy an important niche in healthy animals. Either the bacteria keep out other types of bacteria just by their presence, or they make compounds that would fight off bacteria that could prevent healing or cause infection, Grice says. “If you leave that niche wide open, it leaves room for something else to come in,” she says.

Grice’s team also found different immune responses to the wounds. Diabetic mice make altered levels of antimicrobial compounds and of immune and inflammatory chemicals compared with their healthy siblings.

Grice doesn’t yet know whether the shifts in microbes lead to impaired wound healing or are a result of slow healing or other differences in the skin of diabetics. She hasn’t yet sampled bacteria in diabetic people.

But the study may lead to improved therapies for treating wounds in people who have diabetes.

“Although the enormous population of bacteria on the human body outnumbers even our own cells, their exact contribution in physiology and pathogenesis is ill defined,” says John Lambris, an immunologist at the University of Pennsylvania School of Medicine in Philadelphia. The new study, “provides an important step towards linking the diversity of microbial distribution in diabetic wounds and their role in healing, thus providing a potential therapeutic target.