Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease

Ahmed Moustafa, Weizhong Li, Ericka L. Anderson, Emily H.M. Wong, Parambir S. Dulai, William J. Sandborn, William Biggs, Shibu Yooseph, Marcus B. Jones, J. Craig Venter*, Karen E. Nelson, John T. Chang, Amalio Telenti, Brigid S. Boland

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Objectives:Inflammatory bowel diseases (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), are characterized by a complex pathophysiology that is thought to result from an aberrant immune response to a dysbiotic luminal microbiota in genetically susceptible individuals. New technologies support the joint assessment of host-microbiome interaction.Methods:Using whole genome sequencing and shotgun metagenomics, we studied the clinical features, host genome, and stool microbial metagenome of 85 IBD patients, and compared the results to 146 control individuals. Genetic risk scores, computed on 159 single nucleotide variants, and human leukocyte antigen (HLA) types differentiated IBD patients from healthy controls.Results:Genetic risk was associated with the need for use of biologics in IBD and, modestly, with the composition of the gut microbiome. As compared with healthy controls, IBD patients had hallmarks of stool microbiome dysbiosis, with loss of a diversified core microbiome, enrichment and depletion of specific bacteria, and enrichment of bacterial virulence factors.Conclusions:We show that genetic risk may have a role in early risk stratification in the care of IBD patients and propose that expression of virulence factors in a dysbiotic microbiome may contribute to pathogenesis in IBD.

Original languageEnglish (US)
Article numbere132
JournalClinical and translational gastroenterology
Volume9
Issue number1
DOIs
StatePublished - Jan 18 2018
Externally publishedYes

ASJC Scopus subject areas

  • Gastroenterology

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