The microbiome is emerging as a prominent player affecting human health, and associated with various diseases. Understanding the roles that the microbiome plays in health and diseases and how it reacts to external factors, such as drugs, requires not only to assess its compositions but also its functional changes. Metaproteomics measures quantitative functional changes in the microbiome and therefore will be an important tool to studies the human microbiome. The microbiome is very complex and new tools and software are needed to elucidate its function. We are developing new metaproteomics tools to study the microbiome and are applying these tools to study host-microbiome interactions and microbiome-drug interactions. Bioinformatics is key to the development of metaproteomics. Our lab introduced in 2017 MetaLab to identify and quantify peptides/proteins from gut microbiome. We will launch version 2.0 of MetaLab and iMetaLab a HUPO. We are also interested in the development of in vitro assays to rapidly assess the effects of compounds on individual microbiome. We will present recent development of an in vitro microbiome assay coupled to metaproteomics to understand the effects of different compounds on individual human microbiomes.