Mucosal host-microbe interactions associate with clinical phenotypes in inflammatory bowel disease

Area of Science:

• Gastroenterology
• Microbiology
• Immunology

Background:

• Disrupted host-microbe interactions at the mucosal level are critical in Inflammatory Bowel Disease (IBD) pathophysiology.
• Understanding these interactions is key to developing targeted therapies.

Purpose of the Study:

• To comprehensively examine the crosstalk between mucosal gene expression and microbiota in IBD patients.
• To identify specific host-microbe interactions associated with disease subtypes and treatments.

Main Methods:

• Transcriptomic (RNA-seq) and microbial (16S-rRNA-seq) profiling of 697 intestinal biopsies from IBD patients and controls.
• Analysis of transcript-bacteria interactions to identify inflammation-related pathways linked to specific bacteria.

Main Results:

• Mucosal gene expression in IBD is influenced by location and inflammation, while microbiota composition is highly individual.
• Specific bacterial abundances correlate with distinct gene expression patterns (e.g., Bifidobacterium with fatty acid metabolism, Bacteroides with metallothionein signaling).
• Distinct transcriptional networks associated with specific bacteria were identified in fibrostenotic Crohn's disease and in patients treated with TNF-α antagonists.

Conclusions:

• Context-specific mucosal host-microbe interactions are present in IBD.
• Altered inflammation-associated gene-taxa modules are particularly evident in fibrostenotic CD and patients on TNF-α antagonists.
• These findings support microbiota-directed precision medicine for IBD.