Effects of meglumine antimoniate and allopurinol treatment on the fecal microbiome profile in dogs with leishmaniosis.

Background: The combination of meglumine antimoniate and allopurinol is considered one of the most effective treatments for canine leishmaniosis caused by Leishmania infantum. This study investigated the effects of this treatment on the gut microbiome of 10 dogs from Spain, Portugal, and Italy via fecal shotgun metagenomic sequencing over six months.

Methods: Dogs were sampled at baseline (BL), after one month of combined treatment with meglumine antimoniate and allopurinol (M1) and after six months of allopurinol treatment (M6). Fecal samples had their total DNA extracted and sequenced by Illumina sequencing. Posteriorly, a microbiome analysis was conducted to analyze bacterial abundance, diversity and enrichment.

Results: The gut microbiome of Leishmania-infected dogs (BL) is dominated by Prevotella, Collinsella, Bacteroides, and Blautia, with individual variability being the primary determinant of microbiome composition. No significant changes in alpha diversity (Shannon index, gene number) or beta diversity (Bray-Curtis dissimilarity, UniFrac distance) were detected between pre- and post-treatment time points, suggesting that treatment with meglumine antimoniate and allopurinol does not disrupt the gut microbiota. Minor trends in taxonomic shifts were noted, with slight increases in Bifidobacterium pseudocantenulatum, Collinsella tanakaei, and Slackia piriformis after treatment, but these changes were not statistically significant after correction for multiple testing. Linear discriminant analysis and multivariable modeling confirmed that the microbial community structure was resilient to treatment effects. Individual-specific microbiome differences in diversity accounted for 52% of the observed variability, underscoring the personalized nature of the gut microbiota in dogs. Importantly, no adverse microbiome disruptions were detected, even with prolonged allopurinol use.

Conclusions: This study highlights the robustness of the canine gut microbiome during antileishmanial therapy and highlights the use of meglumine antimoniate and allopurinol without compromising gut microbial diversity or health. Further studies with larger cohorts are recommended to confirm these findings and explore the functional roles of the gut microbiota in modulating immune responses in Leishmania-infected dogs.