Microbiome/Metabolic Syndrome/Diabetes and CVD

Abstract

We have carried out taxonomic profiling of gut microbiota in a population of about 100 commercially available inbred strains of mice termed the Hybrid Mouse Diversity Panel (HMDP). This panel has been developed as a systems genetics resource and can be used for high resolution association mapping of complex traits. When maintained under controlled environmental conditions, the gut microbiota composition exhibits high heritability in the HMDP as calculated using a linear mixed model assuming additive genetic effects. Genome‐wide association analysis with informative SNPs identified significant loci in the mouse genome associated with relative abundances of specific taxa. The HMDP mice have been typed for a number of cardiovascular, metabolic, and other clinical traits, allowing correlation analysis of gut microbiota composition with clinical traits. Some of these associations, such as the association between Akkermansia muciniphila levels and high fat diet response, have subsequently been confirmed in published experimental studies. A number of novel associations are presently being tested using co‐fostering of different inbred strains or experimental introduction of cultured bacterial species. A variety of diets have been studied across the HMDP. In conclusion, studies of natural variations in gut microbiota composition in mice may help identify regulatory host factors as well as providing a global view of the relationships between microbiota and clinically relevant traits.