Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease

Area of Science:

• Microbiome Research
• Immunology
• Gastroenterology

Background:

• Abnormal immune responses to the gut microbiome are implicated in inflammatory bowel disease (IBD).
• Understanding host-microbe interactions is crucial for IBD pathogenesis.

Purpose of the Study:

• To investigate the relationship between the gut microbiome and pediatric inflammatory bowel disease (PIBD).
• To identify specific bacterial clades and strains associated with PIBD.
• To explore the role of anatomical site and strain-specific phenotypes in IBD.

Main Methods:

• Combined high-resolution, culture-based shotgun metagenomic sequencing and host transcriptomics.
• Analyzed samples from three intestinal sites (terminal ileum, cecum, rectum) of PIBD patients and controls.
• Established a cohort-specific bacterial culture collection and performed strain-specific in vitro validation.

Main Results:

• Identified functionally distinct Enterococcus clades associated with either IBD or health using phylogeny-based metagenomic analysis.
• Demonstrated differences in bacterial strain cytotoxicity and inflammatory signaling in intestinal epithelial cells.
• Observed colonic mucosa-specific responses in patients with IBD, correlating with strain-specific phenotypes.

Conclusions:

• Specific Enterococcus clades and strains are associated with PIBD.
• Strain-specific bacterial phenotypes influence host inflammatory responses.
• Anatomical site is critical for understanding dysregulated host-bacterial interactions in IBD.