A recent study has revealed that a perturbed skin microbiome can be contagious and promote inflammation.
Even in healthy individuals, the skin plays host to a menagerie of bacteria, fungi and viruses. Growing scientific evidence suggests that this lively community, collectively known as the skin microbiome, serves an important role in healing, allergies, inflammatory responses and protection from infection.
Researchers at the University of Pennsylvania showed for the first time that, not only can infection with the Leishmania parasite alter the skin microbiome of affected mice, but this altered microbial community can be passed to uninfected mice that share a cage with the infected animals.
Mice with the perturbed microbiome, or dysbiosis, had heightened inflammatory responses and more severe disease when they were subsequently infected with Leishmania.
"To my knowledge, this is the first case where anyone has shown that a pre-existing skin microbiome can influence the outcome of an infection or a disease," said co-senior author Elizabeth Grice. "This opens the door to many other avenues of research."
In addition, when the researchers examined samples from human Leishmania patients, they found similar patterns of dysbiosis as in the infected mice, a hint that the findings may extend to people.
"The transmission of dysbiosis in the skin from one animal to another is a key finding," said co-senior author Phillip Scott. "And the fact that we saw similar patterns of dysbiosis in humans suggests there could be some very practical implications of our work when it comes to treating people with leishmaniasis."
Cutaneous leishmaniasis is a tropical disease caused by a parasite and transmitted by the bite of a sand fly. The disease results in sores on the skin, which can sometimes become severe and disfiguring. There is no vaccine for the disease and the limited drugs available often fail to provide a complete cure.
Curious about the influence of the skin microbiome on the disease, the Penn-led team swabbed the skin of 44 Leishmania patients, analyzing the microbiota not only of their lesions but also the area around them and a portion of skin on the opposite side of the bodies as the lesion. They noticed that the lesion samples contained less bacterial diversity than the samples of other skin sites. But not all of them were the same; they found three distinct community types: one dominated by Staphylococcus, one by Streptococcus and one that was mixed.
"I think an important next step will be to see if this sharing of microbiota occurs in people, and whether that could be a factor in affecting the severity of infections in humans," Grice said.
A final question was to determine whether this naturally transmitted dysbiosis would predispose the uninfected animals' response to an enhanced inflammatory response. And indeed, when infected with Leishmania, these mice had more severe inflammation and skin ulcers than mice with unperturbed skin microbiota. In a more general assay, the researchers used a contact hypersensitivity assay, which uses a skin irritant to elicit an immune response, on the mice that had been housed with Leishmania-infected mice. These dysbiotic mice, too, had a heightened inflammatory response.
To follow up on their findings, the researchers hope to examine whether sharing of a dysbiosis occurs in other infections and whether the resulting alteration in skin microbiota affect processes such as wound healing.
In addition, the researchers hope to determine whether there is a connection between the type of skin microbiome present in Leishmania lesions and the severity of disease, or the responsiveness to treatment.
If true, "this may make us rethink the role of antibiotics in treating leishmaniasis," Scott said.
The findings are published in the journal Cell Host & Microbe.