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Characterization of fecal mycobiota reveals yeast-host coevolution in pediatric Crohn’s disease

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Characterization of fecal mycobiota reveals yeast-host coevolution in pediatric Crohn’s disease

Carlotta De Filippo1, Monica Di Paola2, Lisa Rizzetto1, Irene Stefanini1, Luisa Berná2, Matteo Ramazzotti3, Leonardo Dapporto4,5, Damariz Rivero2, Ivo G Gut6, Jean-Luc Legras7,8,9, Cristina Massi-Benedetti10, Antonella De Luca10, Luigina Romani10 , Paolo Lionetti2, Duccio Cavalieri1

1

Edmund Mach Foundation, Research and Innovation Centre, San Michele all’Adige (Trento), Italy; 2Department of Neuroscience, Psychology, Drug Research and Child's health University of Florence, Florence, Italy; 3Department of Biochemistry, University of Florence, Italy; 4 Department of Evolutionary Biology University of Florence, Florence, Italy; 5 Department of Agricultural Biotechnology, University of Florence, 50144,

Florence, Italy; 6CNAG Centre Nacional d’Anàlisi Genòmica, 08028 Barcelona, Spain

7

INRA (Institut National de la Recherche Agronomique),UMR1083 (Unité Mixte de Recherche Sciences pour l’Oenologie), F-34060 Montpellier, France ; 8

Montpellier SupAgro, UMR1083 (Unité Mixte de Recherche Sciences pour l’Oenologie), F-34060 Montpellier, France ; 9 Université Montpellier I, UMR1083 (Unité Mixte de Recherche Sciences pour l’Oenologie), F-34060, Montpellier, France; 10

Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy

At variance with the well-recognized role of intestinal bacterial communities, the fungal contribution on the balance between health and disease is still debated. Here we report that gut mycobiota of 93 healthy and Inflammatory Bowel Disease (IBD) affected children is enriched in non-pathogenic species, including Ascomycetes. Notably, phylogenetic analysis of Saccharomyces cerevisiae fecal isolates provided evidence for co-evolution of strains gut-specific with the host, clustering separately with respect to S.

cerevisiae isolated worldwide from different sources. Through cytokine production, S. cerevisiae isolates differently contribute to local immune homeostasis. Whole genome

sequencing of 21 fecal strains discovered wild-domestic mosaic populations evolved in the human gut, unveiling selection in specific loci regulating sporulation and pseudohypal formation as responsible for the strains’ immunomodulatory properties. Also we show that the definition of pathogenic species should be reassessed investigating the variability of the pathogenic profiles of specific strains, corroborating the idea that depending on the genetic makeup of the host and of the yeast, even S. cerevisiae could be seen as an opportunistic pathogen.

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POSTER TOPICS ( delete the options you are not interested in) A –Microbial Genetics and Genomics

B – Environmental and Industrial Microbiology

C – Interactions between microbes-viruses and their hosts

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