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

Gemma L. D'Adamo, Michelle Chonwerawong, Linden J. Gearing, Vanessa R. Marcelino, Jodee A. Gould, Emily L. Rutten, Sean M. Solari, Patricia W.R. Khoo, Trevor J. Wilson, Tamblyn Thomason, Emily L. Gulliver, Paul J. Hertzog, Edward M. Giles, Samuel C. Forster

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1 Citation (Scopus)

Abstract

Abnormal immune responses to the resident gut microbiome can drive inflammatory bowel disease (IBD). Here, we combine high-resolution, culture-based shotgun metagenomic sequencing and analysis with matched host transcriptomics across three intestinal sites (terminal ileum, cecum, rectum) from pediatric IBD (PIBD) patients (n = 58) and matched controls (n = 42) to investigate this relationship. Combining our site-specific approach with bacterial culturing, we establish a cohort-specific bacterial culture collection, comprising 6,620 isolates (170 distinct species, 32 putative novel), cultured from 286 mucosal biopsies. Phylogeny-based, clade-specific metagenomic analysis identifies key, functionally distinct Enterococcus clades associated with either IBD or health. Strain-specific in vitro validation demonstrates differences in cell cytotoxicity and inflammatory signaling in intestinal epithelial cells, consistent with the colonic mucosa-specific response measured in patients with IBD. This demonstrates the importance of strain-specific phenotypes and consideration of anatomical sites in exploring the dysregulated host-bacterial interactions in IBD.

Original languageEnglish
Article number101124
Number of pages14
JournalCell Reports Medicine
Volume4
Issue number7
DOIs
Publication statusPublished - 18 Jul 2023

Keywords

  • cell death
  • Enterococcus
  • epithelial cells
  • gastrointestinal tract
  • host-microbe interactions
  • inflammatory bowel disease
  • metagenomic
  • microbiome
  • pediatric IBD
  • ulcerative colitis

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