PROJECT SUMMARY Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction that affects up to 20% of school children worldwide. Dietary interventions, particularly those removing fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAP) carbohydrates from the diet, may be helpful in both adults and children with IBS. Unfortunately, there are significant practical and potential health challenges (e.g., unintended weight loss) to following a FODMAP restriction diet. Identifying new therapies beyond dietary restriction alone for FODMAP-induced symptoms, particularly in children, is needed. Fructans are a type of FODMAP that are naturally occurring, abundant in our diet, and are a major focus of restriction in the low FODMAP diet. After ingestion, fructans arrive in the colon essentially intact where they are fermented rapidly by gut microbiota. We identified that a subset (~50%) of children with IBS are fructan- sensitive meaning they experience worsening abdominal pain when fed fructans. The biggest distinguishing feature between those who are fructan-sensitive vs. fructan tolerant (do not develop worsening pain) is a distinct microbial composition and fermentation pattern. These data suggest fructan fermentation by the gut microbiota is an important factor in determining whether subsequent gastrointestinal symptoms develop. Psyllium is a viscous, soluble, poorly fermented fiber that we demonstrated in children with IBS decreases abdominal pain frequency. However, psyllium efficacy is modest and the mechanism by which it ameliorates IBS is unknown. Importantly, a recent study reported that psyllium administered concurrently with fructans affected fructan fermentation: Adults who consumed fructans with psyllium (vs. fructans alone) had both decreased colonic gas production and overall colonic volume. This means psyllium represents a potentially important clinical intervention that may avoid the need for dietary fructan (and other FODMAPs) restriction and needs to be tested. To begin to investigate psyllium treatment for FODMAP (fructan)-induced pain, we will first identify children with IBS who are fructan-sensitive using our established randomized crossover protocol. Following a two-week baseline period In those who are fructan-sensitive (n=45), we then propose a two-week double-blind randomized parallel-group study in which participants receive either psyllium (1 g/year of age or 0.5 g/year of age per day) with fructans or a placebo (glucose) with fructans. Our central hypothesis is that psyllium given with fructans to fructan-sensitive children with IBS will decrease colonic fermentation of fructans and fructan-induced gastrointestinal symptoms. The Specific Aims of the project are to: 1) Investigate the effect of psyllium at two doses given with a fructan meal on microbial fructan fermentation; 2) Determine the effect of psyllium given with a fructan meal on fructan-induced gastrointestinal symptoms. The know...