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

Gut Microbes. 2021 Jan-Dec;13(1):1930871. doi: 10.1080/19490976.2021.1930871.

Abstract

The etiology of Crohn's disease (CD) is multifactorial. Bacterial and fungal microbiota are involved in the onset and/or progression of the disease. A bacterial dysbiosis in CD patients is accepted; however, less is known about the mycobiome and the relationships between the two communities. We investigated the interkingdom relationships, their metabolic consequences, and the changes in the fungal community during relapse and remission in CD.Two cohorts were evaluated: a British cohort (n = 63) comprising CD and ulcerative colitis patients, and controls. The fungal and bacterial communities of biopsy and fecal samples were analyzed, with the fecal volatiles; datasets were also integrated; and a Dutch cohort (n = 41) comprising CD patients and healthy controls was analyzed for stability of the gut mycobiome.A dysbiosis of the bacterial community was observed in biopsies and stool. Results suggest Bacteroides is likely key in CD and may modulate Candida colonization. A dysbiosis of the fungal community was observed only in the Dutch cohort; Malassezia and Candida were increased in patients taking immunosuppressants. Longitudinal analysis showed an increase in Cyberlindnera in relapse. Saccharomyces was dominant in all fecal samples, but not in biopsies, some of which did not yield fungal reads; amino acid degradation was the main metabolic change associated with CD and both bacteria and fungi might be implicated.We have shown that Bacteroides and yeasts may play a role in CD; understanding their role and relationship in the disease would shed new light on the development and treatment of CD.

Keywords: Crohn’s disease; metabolome; microbiome; mycobiome; volatile organic compound.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification*
  • Child
  • Cohort Studies
  • Crohn Disease / microbiology*
  • Dysbiosis / microbiology
  • Feces / microbiology
  • Female
  • Fungi / classification
  • Fungi / genetics
  • Fungi / isolation & purification*
  • Gastrointestinal Microbiome*
  • Humans
  • Male
  • Middle Aged
  • Young Adult

Grants and funding

This work was funded by Crohn’s and Colitis UK (CCUK) (grant number M/15/4, principal investigator CSJP). UZI was funded by the NERC IRF NE/L011956/1.