His research group specializes in understanding how the human microbiome is involved in health and disease. He has a particular interest in the role of the microbiome in colorectal cancer and Clostridium difficile infections. His research group pursues a community-based approach where they seek to understand how entire microbial communities and subsets of those communities could be used to classify people by their health status or risk of disease instead of trying to link individual bacteria with pathogenesis. To support these efforts, Schloss's team has developed several prominent computer programs for analyzing the DNA sequence data generated from microbial ecology studies. The ability to bridge biology and computational sciences has allowed Schloss to leave a positive impact on a diverse array of important research questions in the field of microbial ecology.