Crohn’s Disease (CD) is a chronic and debilitating disorder with peak incidence in the second and third decades of life. While considerable progress has been made in optimizing medications to achieve remission, relapse is common and unpredictable. Altered microbiota likely drive gut inflammation and clinical relapses. Microbiota-accessible dietary carbohydrates with beneficial health effects, known as “prebiotics,” hold promise for restoring healthy gut microbiota in CD and preventing clinical relapse. Here, we propose completion of the first studies of the prebiotic human milk oligosaccharide, 2’-fucosyllactose (2’-FL), for maintaining remission in CD. Our overarching hypothesis is that 2’-FL supplementation in CD will be safe and well tolerated, while increasing fecal Bifidobacterium abundance and butyrate in a dose dependent manner. We will test this hypothesis by completing a randomized, placebo-controlled dose-ranging study which began enrollment during the tenure of the current award and includes the following Aims: Aim 1. Define dose dependent safety and tolerability of 2’-FL as a dietary supplement in CD. We will test 1g or 5g 2’-FL compared to 2 gm dextrose placebo as a daily dietary supplement in pediatric and young adult CD patients in stable remission receiving infliximab or adalimumab anti-TNF therapy. Safety and tolerability will be assessed using validated clinical disease activity and gastrointestinal symptom rating indices, and fecal calprotectin. Aim 2. Define dose dependent efficacy of 2’-FL as a dietary supplement in CD. We will utilize our established fecal metagenomic and metabolite profiling assays to test the effect of a range of 2’FL doses upon the gut microbial community and associated metabolic functions with a focus upon butyrate production. Efficacy will be assessed by determining the dose dependent effect of 2’-FL upon increased fecal Bifidobacterium and butyrate abundance. We will account for FUT2 secretor status and dietary fiber intake in the analysis. These studies will have a high impact in the field by providing critical phase I/IIa safety and efficacy data in support of a phase III RCT using our NIH-supported CD clinical research network to test the efficacy of 2’-FL in directly modulating beneficial microbiota and thereby enhancing sustained clinical remission and mucosal healing. Ultimately the proposed studies will promote a fundamental shift in clinical practice towards personalized microbial therapeutic interventions.