Microbiome-driven drug discovery holds great promise for therapeutic development. However, identification of disease-associated microbiome-host interactions are challenging, owing largely to the complexity of a diverse community and the myriad of direct and indirect interactions through which the microbiome can influence its host. Moreover, inflammatory bowel disease (IBD) is a heterogeneous disease with a complex diagnosis, and multiple etiologies, pathologies, and treatment responses. Finding robust associations between IBD and the microbiome has proven difficult.