Cutaneous leishmaniasis, a parasitic disease caused by Leishmania major, is a widely frequent form in humans. To explore the importance of the host gut microbiota and to investigate its changes during L. major infection, two different groups of mouse models were assessed. The microbiome of two parts of the host gut-ileum and colon-from infected and non-infected mice were characterised by sequencing of 16S rDNA using an Ion Torrent PGM platform. Microbiome analysis was performed to reveal changes related to the susceptibility and the genetics of mice strains in two different gut compartments and to compare the results between infected and non-infected mice. The results showed that Leishmania infection affects mainly the ileum microbiota, whereas the colon bacterial community was more stable. Different biomarkers were determined in the gut microbiota of infected resistant mice and infected susceptible mice using LEfSe analysis. Lactobacillaceae was associated with resistance in the colon microbiota of all resistant mice strains infected with L. major. Genes related to xenobiotic biodegradation and metabolism and amino acid metabolism were primarily enriched in the small intestine microbiome of resistant strains, while genes associated with carbohydrate metabolism and glycan biosynthesis and metabolism were most abundant in the gut microbiome of the infected susceptible mice. These results should improve our understanding of host-parasite interaction and provide important insights into the effect of leishmaniasis on the gut microbiota. Also, this study highlights the role of host genetic variation in shaping the diversity and composition of the gut microbiome. KEY POINTS: • Leishmaniasis may affect mainly the ileum microbiota while colon microbiota was more stable. • Biomarkers related with resistance or susceptibility were determined in the gut microbiota of mice. • Several pathways were predicted to be upregulated in the gut microbiota of resistant or susceptible mice.

Department of Cardiology 1 Coronary and Peripheral Vascular Disease Heart Failure University Hospital Münster Westfälische Wilhelms Universität Münster Germany

Department of Medical Genetics 3Rd Faculty of Medicine Charles University Ruská 87 100 00 Prague 10 Czech Republic

Department of Molecular and Cellular Biology Roswell Park Comprehensive Cancer Center Buffalo NY 14263 USA

Faculty of Biomedical Engineering Czech Technical University Prague Namestí Sitna 3105 272 01 Kladno Czech Republic

Laboratory of Anaerobic Microbiology Institute of Animal Physiology and Genetics of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

Laboratory of Molecular and Cellular Immunology Institute of Molecular Genetics of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

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Improving reproducibility and translational potential of mouse models: lessons from studying leishmaniasis

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