Variation in clinical response to 5-aminosalicylic acid (5-ASA) has been attributed in part to its inactivation by gut microbes. Recently, in the Inflammatory Bowel Disease (IBD) Multi’omics Database (IBDMDB), a multicenter year-long cohort of 100+ participants with IBD, we identified 12 gut microbial enzymes from two protein families that convert 5-ASA to N-acetyl 5-ASA, a compound that lacks anti-inflammatory effects. Within the IBDMDB, we then found that a subset of these enzymes was cross-sectionally linked with greater risk of treatment failure, defined by corticosteroid use.