Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract that affects millions worldwide. Though research has made strides in identifying factors contributing to IBD pathogenesis—most prominently immune dysregulation and gut microbiome composition—the causes and mechanisms of IBD remain largely unknown. Genome-wide association studies (GWAS) have successfully identified over 240 loci in the human genome associated with IBD, providing crucial insights into disease susceptibility. However, GWAS studies primarily capture IBD from the perspective of human genetics, completely overlooking the essential role of the microbiome in disease causation. Therefore, we propose conducting a Microbialwide Association Study (MWAS) based on a clinical study of 5,000 patients at MGH, which represents the largest microbiome metagenomic dataset of IBD patients to date.

This project aims to analyze the evolution of bacterial genes and mutations in IBD patients and their corresponding interactions with the human gut, using an unprecedented level of detail to explore the fundamental question: “What causes IBD?”