Inter-kingdom relationships in Crohn's disease explored using a multi-omics approach

Area of Science:

• Gastroenterology
• Microbiology
• Immunology

Background:

• The etiology of Crohn's disease (CD) is multifactorial, involving both bacterial and fungal microbiota.
• While bacterial dysbiosis in CD is recognized, the role of the mycobiome and its interplay with bacteria remains less understood.
• Investigating interkingdom relationships and metabolic consequences is crucial for understanding CD pathogenesis.

Purpose of the Study:

• To investigate interkingdom relationships between bacteria and fungi in Crohn's disease.
• To explore the metabolic consequences of these microbial interactions.
• To analyze changes in the fungal community during CD relapse and remission.

Main Methods:

• Analysis of fungal and bacterial communities in biopsy and fecal samples from two cohorts (British and Dutch).
• Fecal volatile analysis and dataset integration.
• Longitudinal analysis of the gut mycobiome stability in CD patients.

Main Results:

• Observed bacterial dysbiosis in both biopsies and stool samples.
• Bacteroides may play a key role in CD, potentially modulating Candida colonization.
• Fungal dysbiosis was noted in the Dutch cohort, with increased Malassezia and Candida in patients on immunosuppressants; Cyberlindnera increased during relapse.
• Saccharomyces dominated fecal samples, but not biopsies.
• Amino acid degradation was the primary metabolic alteration in CD, implicating both bacterial and fungal communities.

Conclusions:

• Bacteroides and yeasts are implicated in Crohn's disease.
• Understanding the role and relationship between these microbes can provide new perspectives on CD development.
• This research highlights potential therapeutic targets for Crohn's disease.