Updated project metadata. We developed an approach named Rapid Assay of Individual Microbiome (RapidAIM) to screen xenobiotics against individual microbiomes. To evaluate technical reproducibility, we tested 43 compounds against an individual's microbiome. The individual microbiome is cultured in triplicates in 96-well plates for 24 hours and the samples are then analyzed using a metaproteomics-based analytical approach to gain functional insight into the individual microbiomes responses following drug treatments.The tested compounds significantly affected overall microbiome abundance, microbiome composition and functional pathways at multiple taxonomic levels. The microbiome responses to berberine, metformin, diclofenac, fructooligosaccharide and most antibiotics were consistent among most individual microbiomes. Interestingly, most of our tested NSAIDs, statins, and histamine-2 blockers induced individually distinct responses. Our workflow offers an effective solution to systematically study the effects of many different compounds on individual microbiomes.