Obesity is currently a worldwide epidemic that has serious consequences for health. It has been suggested that the gut microbiota can influence body weight, e.g., by producing shortchain fatty acids (SCFA), which are substrates for the host and induce the release of satiety hormones (e.g., PYY). To test the potential prebiotic effect of cassava bagasse (a by-product from cassava flour and starch production) in vitro fermentation experiments were performed using fecal microbiota originating from lean and obese subjects in a validated model of the colon (TIM-2). The microbial composition and production of microbial metabolites were analysed. Cassava was found to modulate the microbiota composition, since it stimulated the growth of the genera Bifidobacterium and Roseburia. The production of SCFA was similar to that for inulin (positive control). Although supplementary in vivo studies with cassava bagasse are needed, this study shows for the first time the prebiotic potential of cassava bagasse.