Abstract

Historically, Trichophyton rubrum has been identified as the causative agent of the disease, Tinea pedis. Treatment options focus on the use of antifungals; however, antifungals have modest efficiency for clearing T. rubrum with high rates of reinfection and disease reoccurrence. Here we propose that T. pedis is not a simple fungal infection but a complex dysbiosis characterized by changes of the fungal and bacterial profile of the microbiome, with Trichophyton being an indicator of the disease. In this study, we used metagenomic sequencing to compare the microbiome composition of the interdigital toe web-space, nail bed, and plantar aspect in a population of individuals with T. pedis simple (n=26), T. pedis complex (n=25), and T. pedis moccasin (n=25) against 33 healthy volunteers and their matching anatomical sites. Metagenomic sequencing demonstrated differences in beta diversity and key species distinctions between diseased (T. pedis) and healthy states. We found that beta diversity differs greatly between these two groups, and that the microbiomes of individuals with T. pedis were significantly more similar to each other than the micobiomes of healthy individuals. There are also robust marker species denoting both T. pedis and healthy states. Specifically, Trichophyton was found in both healthy and diseased subjects but higher in abundance for T. pedis subjects. Other fungi had similar co-associations with the disease state. Bacterial co-occurrences with Corynebacterium resistens had the highest association in subjects with T. pedis, while Staphylococcus hominis and S. epidermidis were significantly higher in healthy individuals as compared to individuals with T. pedis. These results indicate that T. pedis is not a strict infection model of disease, but rather a dysbiosis associated with a community of organisms. A therapeutic approach to repair the dysbiosis has the potential for a more effective diagnostic and treatment plan for patients, with better long-term outcomes.

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