Abstract

BackgroundHost-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.MethodsDextran 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.ResultsWhile 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.ConclusionsFungal 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.

Highlights

  • Host-microbe balance maintains intestinal homeostasis and strongly influences inflammatory conditions such as inflammatory bowel diseases (IBD)

  • We showed that the presence of bacterial species belonging to the Enterobacteriaceae family greatly influences the fitness of C. albicans and S. boulardii in the gastrointestinal tract and further determines how these fungi modulate the outcome of intestinal inflammation

  • C. albicans and S. boulardii have opposite effects on DSS-induced colitis in untreated mice but lose their effects after broad-spectrum antibiotic treatment We first evaluated the effect of daily administration of C. albicans and Saccharomyces boulardii CNCM I-745 on dextran sodium sulfate (DSS)-induced colitis (Fig. 1a)

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Summary

Introduction

Host-microbe balance maintains intestinal homeostasis and strongly influences inflammatory conditions such as inflammatory bowel diseases (IBD). We focused on bacteria-fungi interactions and their implications on intestinal inflammation, a poorly understood area. The mammalian GIT is colonized by diverse commensal microbial communities consisting of bacteria, fungi, and viruses [1]. Alteration of the composition of function of the gut microbiota, i.e., dysbiosis, has been associated with several human diseases and with inflammatory bowel disease (IBD). C. albicans, which is the most prevalent fungus in the human intestinal microbiota [14, 15], shows improved colonization in inflammatory context and simultaneously worsens intestinal inflammation in a murine colitis model [16]

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