Interindividual variability in responses to prebiotic fibers is an obstacle to improving health via microbiome modulation. Recent advances in ex vivo screening have enabled the personalized selection of prebiotics. This approach, when integrated with meta-omic analyses, hold the potential to unveil microbial factors underlying interindividual variability. Furthermore, most prebiotic-based therapies target butyrate production, a process which is dysregulated in conditions like inflammatory bowel disease (IBD). Other metabolites and functional pathways are rarely considered as targets of microbiome modulation. We conducted high-throughput microbiome culturing using stool samples obtained from 15 pediatric IBD patients with a panel of 9 different resistant starches. After an 18 h culture, we performed meta-omic analyses (16S metagenomics, semi-targeted metabolomics, and shotgun metaproteomics) to examine changes to the microbiomes. Parallel group-level and individual-level analyses revealed starch- and individual-specific changes in fermentation, taxonomic diversity, and functional output. Microbiome responses principally differed by proteins involved in amino acid and nucleic acid metabolism, the metabolite uridine, and Clostridia. We also highlight individualized resistant starch-driven increases in reportedly anti-inflammatory metabolites, such as alpha-ketoglutaric acid, and preferential production of acetate over butyrate. Our ex vivo findings reinforce recent calls to individualize prebiotic therapies, particularly in clinically relevant populations. We present evidence to reconceptualize the beneficial properties of prebiotics to include fermentation by-products beyond butyrate.