In a new study, researchers at the University of Pennsylvania have shown 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.

The findings were published in the journal Cell Host & Microbe.

“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 Elizabeth Grice, co–senior author and assistant professor in the departments of Dermatology and Microbiology in Penn’s Perelman School of Medicine. “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.

Grice and Scott collaborated with researchers from Penn Medicine and Penn Vet, including lead author Ciara Gimblet, a Ph.D. student in Scott’s lab, and colleagues from Brazil’s Oswaldo Cruz Foundation.

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.

To get a clearer picture of how these microbiome shifts were connected to the disease, the researchers turned to a mouse model of Leishmania infection. Mirroring the findings in humans, the team found that infection with the Leishmania parasite induced a change in the skin microbiota in mice. They also found an association between the microbiota community type and disease severity. In mice that eventually resolved their infections, Staphylococcus dominated in the lesions, while Streptococcus was the dominant species in lesions on mice with a persistent, severe form of the disease.

A major discovery was that these shifts in microbiota were transmissible not only to other parts of the same mouse but to cage mates. When they kept mice infected with Leishmania in the same cage as uninfected mice for six weeks, the uninfected mice acquired a perturbed skin microbiome “profile” that resembled the infected mice.

The researchers hope to see whether the sharing of perturbed microbiota happens not just in mouse cages but also in households.

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 Penn researchers will be working with their colleagues in Brazil to further examine the connections between the microbiome and leishmaniasis. Specifically, they 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.