116 Acute inorganic arsenic exposure and antibiotic perturbation of the murine gut microbiome induce interindividual susceptibility to a sepsis-like disease

Objectives/Goals: We investigate how the gut microbiome protects against arsenic toxicity, showing antibiotic perturbation increases toxicity and causes interindividual susceptibility to a sepsis-like disease state in mice. Here, we aim to understand how baseline microbiomes from various mouse vendors impact these outcomes and characterize the observed disease. Methods/Study Population: We developed a novel mouse model where mice are exposed to an antibiotic (cefoperazone) for 2 days, followed by co-exposure to the antibiotic and 100 ppm arsenate. So far, we have evaluated C57BL/6N mice from MSU’s in-house colony, Taconic Biosciences (TAC), and Jackson Labs (JAX), along with C57BL/6J mice from JAX. To determine if the baseline microbiome drives inter-vivarium differences, we established in-house breeding colonies of TAC- and JAX-origin mice at MSU. This allowed us to assess whether, when housed under identical conditions, these mice still show differences in mortality based on their original microbiomes. To characterize the arsenic-induced sepsis-like disease, we performed blood biochemistry assays to quantify the white blood cell populations, and sepsis biomarkers used in clinical settings. Results/Anticipated Results: We observed differences in survival rates between genetically identical mice from MSU (45%), TAC (30%), and JAX (2.5%) in our model. From this, we characterized the baseline composition of the gut microbiomes of these mice and found they were significantly different from each other. We are still awaiting results from our in-house TAC and JAX experiments but expect them to have similar gut microbiome compositions to those directly purchased from TAC and JAX and respond similarly. In our blood biochemistry analysis, we found sick mice presented with low WBC counts and notable biomarkers indicative of liver, heart, and kidney distress. We also anticipate that 16S sequencing results of cecal contents will further support findings by providing evidence of a bacterial infection in the ceca of sick mice. Discussion/Significance of Impact: Collectively, our work demonstrates that antibiotic perturbation of the gut microbiome induces an inter-individual and inter-vivarium susceptibility to an arsenic-induced sepsis-like disease state. This work highlights the importance of considering antibiotic use in the risk assessment of arsenic to better protect the health of those exposed.