IMPACT OF CHEMERIN OR CMKLR1 LOSS ON THE MURINE GUT MICROBIOME

Chemerin is an adipokine with established roles in metabolism and inflammation. The composition and function of gut microbiota has also been shown to impact the development of metabolic and inflammatory diseases such as obesity, diabetes and inflammatory bowel disease. In this study, we assessed the microbiome composition of fecal samples isolated from wildtype, chemerin, and chemerin receptor (CMKLR1) knockout (KO) mice using Illumina-based sequencing. The KO mice and respective wildtype mice used in this study were housed at different universities. While there was no difference in alpha diversity within samples when compared by either facility or genotype, we observed a dramatic difference in the presence and abundance of numerous taxa between facilities. There were minor differences in bacterial abundance between wildtype and chemerin KO mice, but significantly more differences in taxa abundance between wildtype and CMKLR1 KO mice. Specifically, CMKLR1 KO mice exhibited decreased abundance of Akkermansia and Prevotella, which correlated with body weight in CMKLR1 KO, but not wildtype mice. This suggests that chemerin/CMKLR1 signaling influences metabolic processes through effects on the gut microbiome. Furthermore, the dramatic difference in microbiome composition between facilities might contribute to discrepancies in the metabolic phenotype of CMKLR1 KO mice reported by independent groups. Considered altogether, these findings establish a foundation for future studies to investigate the relationship between chemerin signaling and the gut microbiome on the development and progression of metabolic and inflammatory disease.