PROJECT SUMMARY Parent award. The initial parent award (P20-GM103625) allowed the University of Arkansas for Medical Sciences (UAMS) to establish the Center for Microbial Pathogenesis and Host Inflammatory Responses (CMPHIR). The scientific focus of the CMPHIR is on understanding infectious disease from the perspective of diverse microbial pathogens and their impact on the host immunological and inflammatory responses influences the disease process. This theme is based on the premise that understanding the complex interplay between diverse pathogens and their common human host is a prerequisite to maximizing opportunities to manipulate one or both sides of this equation in favor of the desired therapeutic outcome. The project is currently in Phase III (P30-GM145393) with the goal of continuing to support and enhance the critical core facilities to support the growing number of CMPHIR investigators, continue to provide administrative support to promote further growth of the CMPHIR and the career development of its investigators, and promote the transition to a self-sustained Center of Biomedical Research Excellence with the expertise and resources required to address existing and emerging problems in infectious disease. The current proposal for a Team Science Administrative Supplement application is directly in line with the goals of the CMPHIR and that it takes a comprehensive, team-based approach to understanding how the crosstalk between microbiota and the host during antibiotic-induced dysbiosis, so that new therapeutic strategies can be implemented to maintain host homeostasis and mitigate disease risk. It is also a direct reflection of the growth of the CMPHIR in that it brings together three investigators (one current CMPHIR P30 pilot recipient and 2 investigators with various other past COBRE and INBRE ties) with distinct areas of expertise that can collectively take advantage of their specific strengths and cutting edge technologies to comprehensively investigate fundamental disease-related processes of highly consequential bacterial imbalance to an extent that otherwise would not be possible. Research question. Antibiotic (ABX) use has significantly increased by more than 30% in recent years. Although ABX fight infections, they also disrupt commensal microbe communities that are crucial for maintaining homeostasis of various local and distal processes. Microbial imbalance induced by ABX, termed herein as dysbiosis, has many systemic and long-lasting effects on the host including, but not limited to, increased risk of vascular pathologies, e.g., solid tumors. Thus, there is a pressing need to reach a deeper understanding of the crosstalk between microbiota and the host during dysbiosis, so that new therapeutic strategies can be implemented to maintain host homeostasis and mitigate disease risk. The long-term overarching goal of this supplement is to initiate a new line of investigation that brings together multiple scientific disciplines ...