Enterobacteriaceae are essential for the modulation of colitis severity by fungi

Bruno Sovran (1) , Julien Planchais (1) , Sarah Jegou (2, 3) , Marjolene Straube (2, 3) , Bruno Lamas (1) , Jane Mea Natividad (1) , Allison Agus (1) , Louise Dupraz (1) , Jeremy Glodt (1) , Grégory da Costa (1) , Marie-Laure Michel (1) , Philippe Langella (1) , Mathias L. Richard (1) , Harry Sokol (2, 3, 4, 5)

1 AgroParisTech
2 LBM UMR 7203 - Laboratoire des biomolécules
3 CHU Saint-Antoine [AP-HP]
4 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
5 CRSA - Centre de Recherche Saint-Antoine

Background Host-microbe balance maintains intestinal homeostasis and strongly influences inflammatory conditions such as inflammatory bowel diseases (IBD). Here we focused on bacteria-fungi interactions and their implications on intestinal inflammation, a poorly understood area. Methods Dextran sodium sulfate (DSS)-induced colitis was assessed in mice treated with vancomycin (targeting gram-positive bacteria) or colistin (targeting Enterobacteriaceae) and supplemented with either Saccharomyces boulardii CNCM I-745 or Candida albicans. Inflammation severity as well as bacterial and fungal microbiota compositions was monitored. Results While S. boulardii improved DSS-induced colitis and C. albicans worsened it in untreated settings, antibiotic treatment strongly modified DSS susceptibility and effects of fungi on colitis. Vancomycin-treated mice were fully protected from colitis, while colistin-treated mice retained colitis phenotype but were not affected anymore by administration of fungi. Antibacterial treatments not only influenced bacterial populations but also had indirect effects on fungal microbiota. Correlations between bacterial and fungal relative abundance were dramatically decreased in colistin-treated mice compared to vancomycin-treated and control mice, suggesting that colistin-sensitive bacteria are involved in interactions with fungi. Restoration of the Enterobacteriaceae population by administrating colistin-resistant Escherichia coli reestablished both beneficial effects of S. boulardii and pathogenic effects of C. albicans on colitis severity. This effect was at least partly mediated by an improved gut colonization by fungi. Conclusions Fungal colonization of the gut is affected by the Enterobacteriaceae population, indirectly modifying effects of mycobiome on the host. This finding provides new insights into the role of inter-kingdom functional interactions in intestinal physiopathology and potentially in IBD.

Mots clés: enterobacteriaceae; S. boulardii CNCM I-745; C. albicans; colitis; fungi

Mots clés: microbiota

Domaines: Sciences du Vivant [q-bio]

Bruno Sovran, Julien Planchais, Sarah Jegou, Marjolene Straube, Bruno Lamas, et al.. Enterobacteriaceae are essential for the modulation of colitis severity by fungi. Microbiome, 2018, 6, pp.152. ⟨10.1186/s40168-018-0538-9⟩. ⟨hal-01875950⟩