Crohn's disease (CD) is a chronic disease of the digestive tract whose pathogenesis remains not fully understood. Several studies have implicated the gut microbiota as a key player in the onset of gut inflammation. However, most of the data is based on case-control studies comparing patients with established disease with controls, usually healthy individuals. The study by Raygoza Garay and colleagues shows for the first time that changes in the composition of the gut microbiota precede CD onset by up to five years. The authors developed a microbiome risk score using a machine-learning model that included bacterial composition and clinical variables from a large cohort of healthy first-degree relatives of patients with CD. This study provides strong evidence that the alterations of the gut microbiota is causal in CD pathogenesis and suggest that early intervention targeting it may be an appropriate preventive strategy.