This federal Project Grant award of $325,139 from the National Center for Advancing Translational Sciences (NCATS), CFDA No. 93.350, supports a feasibility and proof-of-concept study to explore the use of target-specific polyclonal antibodies to intercept and neutralize bioactive molecules in the gut microbiome of individuals with microbiome-driven inflammation and loss of gut barrier function. The project aims to determine the impact of six protein classes identified as overabundant in metaproteomic surveys of fecal microbiomes of those with inflammatory disorders, and then assess the ability of immunoglobulin Y (IgY) antibodies to neutralize the physiological impacts of these proteins in a human stem-cell-derived in vitro model of colonic epithelia. The long-term objective is to develop a family of Critical Microbiome Pathway Inhibitors (CMPIs) - antibody-based drugs designed to block multiple critical pathways in a coordinated fashion to potentially prevent or treat various microbiome-associated disorders.