Cutaneous leishmaniasis promotes skin microbial dysbiosis and exacerbation of local inflammatory responses.

Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites belongs to the genus Leishmania transmitted to humans by the bite of the infected female sand fly. Increasing evidence suggested that alterations in the skin microbiome may influence local inflammatory responses and disease progression in CL. This study aimed to investigate the microbial community shifts associated with CL lesions using paired lesional and contralateral healthy skin samples from infected individuals (n = 8). Leishmania tropica was identified in all clinical samples by ITS-1 real-time PCR analysis. Microbiome profiling was performed using 16S rRNA gene amplicon sequencing followed by quality filtering, taxonomic classification using Kraken2/Bracken and statistical analysis. Phylum level analysis demonstrated altered microbial composition in lesional skin, with predominance of Proteobacteria. At the genus and species levels, lesional samples exhibited reduced microbial evenness and enrichment of opportunistic bacterial genera, including Stenotrophomonas, Pseudomonas, Acinetobacter, and Staphylococcus. In comparison, contralateral healthy skin indicated dominance of environmental and commensal bacteria such as Luteibacter, Methylobacterium, and Paracoccus, representing a relatively stable microbial community (FDR p ≥ 0.05). Alpha diversity analysis showed reduced microbial diversity in CL infected samples, whereas beta diversity analysis indicated clear difference between CL infected and contralateral skin microbiomes. The findings indicate that CL is associated with localized microbial dysbiosis characterized by altered community structure. These findings highlight the significance of skin microbiome as a contributing factor in CL pathogenesis and suggest that microbiome targeted approach may complement existing therapeutic strategies.