Highlights from

ECCO 2019

European Crohn's and Colitis Organisation's 14th congress

Copenhagen 6-9 March 2019

Novel host-microbiome interactions in inflammatory bowel disease

Scientists from Groningen (the Netherlands) and Boston (USA) performed what they claimed to be the largest, high-resolution, genome–microbiome association study to date using whole-exome sequencing and metagenomics sequencing methods [1]. Disease-specific interactions were explored in the context of inflammatory bowel disease (IBD), including the effect of risk loci and protein-truncating variants.

Whole-exome sequencing of the host genome, and whole-genome shotgun sequencing of faecal samples of 524 IBD patients and 939 controls from a population-based cohort were performed. The interaction between exonic variants, microbial taxa, and metabolic pathways was explored using a four-step approach:

  1. A bidirectional meta-analysis between the 2 cohorts to identify common variants.
  2. A targeted meta-analysis of IBD risk loci and protein-truncating variants (PTVs).
  3. A gene-based burden test to detect rare mutations that affect microbial features.
  4. An interaction analysis to identify IBD-specific microbial quantitative trait loci (mbQTLs).

In 170,000 protein-coding variants and 641 microbial features, 26 associations between genetic variants and gut microbial features (FDR<0.05) were identified. Among common variants, a strong mbQTL was observed for deletion near the IBD-risk IL17REL gene that was correlated to Alistipes indistinctus abundance, known to be decreased in IBD patients. Mutations in an IBD-related gene CYP2D6, a major component of phase I drug metabolism, were associated with decreased bacterial biosynthesis of vitamin K (PWY-5838). The GPR151 gene, which protects against obesity and type II diabetes, was found to be associated with a decrease in bacterial degradation of glucose. The interaction analysis revealed another association between BTNL2 and bacteroides specific to IBD. These results highlight the importance of host genetics in the maintenance of gut microbiome homeostasis critical for prevention of IBD.

Keywords: sequencing

  1. Hu S, et al. ECCO 2019, OP01.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.