Abstract
Chemerin is an adipocyte derived signalling molecule (adipokine) that serves as a ligand activator of Chemokine-like receptor 1(CMKLR1). Chemerin/CMKLR1 signalling is well established to regulate fundamental processes 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, or CMKLR1 knockout mice using Illumina-based sequencing. Moreover, the knockout mice and respective wildtype mice used in this study were housed at different universities allowing us to compare facility-dependent effects on microbiome composition. 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 knockout mice, but significantly more differences in taxa abundance between wildtype and CMKLR1 knockout mice. Specifically, CMKLR1 knockout mice exhibited decreased abundance of Akkermansia and Prevotella, which correlated with body weight in CMKLR1 knockout, but not wildtype mice. This is the first study to investigate a linkage between chemerin/CMKLR1 signaling and microbiome composition. The results of our study suggest 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 knockout 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.
Highlights
The human body is host to a vast number of microbes that include bacteria, fungi, protozoan cells, and viruses, which live in a symbiotic manner encompassing commensal, mutual, and sometimes parasitic relationships, and are collectively termed the microbiota
To investigate the impact of a loss of chemerin or chemokine-like receptor 1 (CMKLR1) expression on microbiome composition, 16S sequencing was performed on DNA isolated from fecal samples collected from female WT (BZ and CS colonies), chemerin KO, and CMKLR1 KO mice
We first examined alpha-diversity using the number of observed operational taxonomic units (OTU) for wildtype (CS and BZ), CMKLR1 KO, and chemerin KO mice (Fig. 1)
Summary
The human body is host to a vast number of microbes that include bacteria, fungi, protozoan cells, and viruses, which live in a symbiotic manner encompassing commensal, mutual, and sometimes parasitic relationships, and are collectively termed the microbiota. Disruption in the normal balance of gut microbial populations, or dysbiosis, results in profound changes in both the activity and function of intestinal microbiota Increasing evidence from both animal models and human observational studies suggest that gut microbial dysbiosis is associated with a wide range of pathological conditions. These include obesity, diabetes, inflammatory bowel disease (IBD), liver disease, cancer, allergy and autoimMune diseases (Barlow, Yu & Mathur, 2015; Marchesi et al, 2015; Zhang et al, 2015)
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