Comparative immunophenotyping of Saccharomyces cerevisiae and Candida spp. strains from Crohn's disease patients and their interactions with the gut microbiome

Monica Di Paola; Lisa Rizzetto; Irene Stefanini; Francesco Vitali; Cristina Massi-Benedetti; Noemi Tocci; Luigina Romani; Matteo Ramazzotti; Paolo Lionetti; Carlotta De Filippo; Duccio Cavalieri

doi:10.1016/j.jtauto.2020.100036

Comparative immunophenotyping of Saccharomyces cerevisiae and Candida spp. strains from Crohn's disease patients and their interactions with the gut microbiome

J Transl Autoimmun. 2020 Jan 26:3:100036. doi: 10.1016/j.jtauto.2020.100036. eCollection 2020.

Authors

Affiliations

¹ Department of Biology, University of Florence, Via Madonna Del Piano 6, 50019 Sesto Fiorentino, Florence, Italy.
² Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, 38010, San Michele All' Adige (Trento), Italy.
³ Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Gibbet Hill Road, CV4 7AL, Coventry, UK.
⁴ Department of Life Sciences and Systems Biology, University of Turin, via Accademia Albertina 13, 10123 Turin, Italy.
⁵ Institute of Biology and Agrarian Biotechnology, National Research Council (IBBA-CNR), Via Moruzzi 1, 56124, Pisa, Italy.
⁶ Department of Experimental Medicine University of Perugia, Piazzale Lucio Severi 1, 06132, Perugia, Italy.
⁷ Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni, 50139, Florence, Italy.
⁸ Department of Neuroscience, Psychology, Drug Research and Child Health, Meyer Children Hospital, University of Florence, Viale G. Pieraccini 6, 50139, Florence, Italy.

Abstract

Investigation of the fungal communities in animal models of Inflammatory Bowel Diseases (IBD) showed a controversial role of Saccharomyces cerevisiae and Candida spp. In health and disease. These conflicting observations could be ascribed to immunogenic differences among co-specific strains. To assess the relevance of intra-strains differences on yeast immunogenicity and impact on the microbiota, we screened S. cerevisiae and Candida spp. Strains isolated from fecal samples of IBD patients. We compared the cytokine profiles, obtained upon stimulation of Peripheral Blood Mononuclear Cells (PBMCs) and Dendritic Cells with different yeast strains, and evaluated the relationship between strain's cell wall sugar amount and immune response. Moreover, the gut microbiota composition was explored in relation to fungal isolation from fecal samples by metabarcoding analysis. The comparison of cytokine profiles showed strain dependent rather than species-dependent differences in immune responses. Differences in immunogenicity correlated with the cell wall composition of S. cerevisiae intestinal strains. Stimulation of human healthy PBMCs with different strains showed a pro-inflammatory IL-6 response counterbalanced by IL-10 production. Interestingly, Crohn's (CD) patients responded differently to "self" and "non-self" strains, eliciting pure Th1 or Th17 cytokine patterns. The differences observed in vitro were recapitulated in vivo, where different strains contributed in dramatically different ways to local epithelial activity and to the inflammation of wild type and Interleukin-deficient mice. Furthermore, we observed that the gut microbiota profiles significantly differentiated according to the presence of Saccharomyces or Candida spp. or the absence of fungal isolates in fecal samples. Our results show the importance to deepen metagenomics and immunophenotyping analyses to the strain level, to elucidate the role of fungal and bacterial communities in health and disease.

Keywords: Candida spp.; Inflammatory bowel disease; Microbiome; Mycobiome; S. cerevisiae.