Irritable bowel syndrome (IBS) is one of the most prevalent functional gut disorders in the world. Partially hydrolyzed guar gum, a low-viscosity soluble fiber, has shown promise in the management of IBS-related symptoms. In this study, we aimed to determine if an individual’s baseline gut microbiota impacted their response to a partially hydrolyzed guar gum intervention. Patients diagnosed with IBS undertook a 90-day intervention and follow-up. IBS symptom severity, tolerability, quality-of-life, and fecal microbiome composition were recorded during this study. Patients with normal microbiota diversity (Shannon index ≥ 3) showed significant improvements to IBS symptom scores, quality-of-life, and better tolerated the intervention compared to patients with low microbiota diversity (Shannon index < 3). Our findings suggest that an individual’s baseline microbiome composition exerts a substantial influence on their response to fiber intervention. Future investigations should explore a symbiotic approach to the treatment of IBS.