Disease signatures in the gut metagenome of a prospective family cohort of inflammatory bowel disease

Inflammatory bowel disease (IBD) is associated with dysbiotic microbiomes. However, whether microbiomes of family members of IBD patients harbour microbial disease signatures of IBD is unknown. Here, we generate shotgun metagenomic data of an IBD family cohort and treatment-naive IBD cases, which we combine with published IBD metagenomes, to perform a meta-analysis of IBD-microbiome associations. Our study reveals microbial shifts that are specific to IBD or IBD subtypes (Crohns disease and ulcerative colitis). We find that IBD cohorts share signatures of association with disease irrespective of geography, and we report novel species-level identifications of microbial taxa that are universal markers of Crohns disease. We further demonstrate that the microbiome of healthy family members at high risk for IBD represent transitional states between the microbiome of unrelated healthy controls and IBD cases, and harbor diversity, compositional and ecological features that are also observed among IBD microbiomes. Overall, our study provides valuable insights into the intricate relationship between the gut microbiome and IBD, with implications for better predicting disease onset among individuals with high susceptibility for IBD.