Host genotypes interact with microbial communities to modulate gene expression in the human intestine

Area of Science:

• Genomics
• Microbiome Research
• Human Genetics

Background:

• Inflammatory Bowel Disease (IBD) involves chronic intestinal inflammation, linked to genetic factors and altered gut microbiome.
• The interplay between host genetics and the gut microbiome in regulating intestinal gene expression and IBD risk is not fully understood.

Purpose of the Study:

• To investigate genotype x microbiome (GxM) interactions in shaping human intestinal gene regulation.
• To determine the contribution of GxM interactions to Inflammatory Bowel Disease (IBD) risk.

Main Methods:

• Analysis of publicly available multi-omics data (host genotype, gene expression, 16S rRNA microbiome) from IBD patients and controls.
• Expression Quantitative Trait Locus (eQTL) mapping and computational fine-mapping to identify causal variants.
• Integration of GxM eQTLs with IBD, Crohn's Disease (CD), and Ulcerative Colitis (UC) GWAS data using Transcriptome-Wide Association Studies and colocalization.

Main Results:

• Identified numerous host genes with eQTLs in both rectum and ileum.
• Discovered significant genotype x microbiome (GxM) interactions affecting host gene expression, involving distinct microbial taxa like butyrate producers and sulfate reducers.
• Found that GxM-regulated variants are associated with host genes implicated in IBD, Crohn's Disease (CD), and Ulcerative Colitis (UC) risk.

Conclusions:

• Demonstrated that host gene expression in the intestine is modulated by microbiome composition.
• Provided evidence that specific microbial taxa can either amplify or buffer genetic predisposition to IBD.
• Suggested potential therapeutic strategies involving targeted microbial interventions based on host genotype to mitigate IBD risk.