Interactions of microbiome, diet, and genetics modulate predispostion to diabetes and metabolic syndrome

The human population is undergoing epidemics of metabolic syndromes, type 2 diabetes, and cardiovascular disease and the reasons for these increases in prevalence are not entirely known.  Scientists understand that this rise may be a combination of genetic risk factors as well as environmental risk factors. Scientists from Harvard, Washington University in St. Louis, and the Helmholtz Center in Germany published a paper in Cell Metabolism investigating three strains of mice and analyzing interactions between host genetics, diet, and the gut microbiota.

They used two strains of mice from the Jackson Laboratory (B6J and 129J) and one strain from Taconic Farms (129T). They Taconic strain is very similar to the 129J strain from Jax however it is given a probiotic, resulting in a difference in its gut microbiome. They also inbred the three strains for several generations to create environmentally normalized mouse groups.

They found that the Taconic 129T mice were similar to the 129J mice in their development of diet induced obesity after a high-fat diet but they only developed mild glucose intolerance in comparison to the Jax mouse strain. After inbreeding these mice for three generations in the same environment, these differences were lost. After analysis including 16s sequencing, the original differences in phenotypes and the changes following inbreeding normalization were a result of microbiome differences and microbiome differences were largely dependent on diet, host genetics, and environmental history.  They also found strong strain-dependent and strain-independent relationships between specific phenotypes and bacterial communities that indicated strong interactions between the microbiome, diet, ancestry and genetics.

This study shows that metabolic syndrome and related conditions is the result of complex interactions between genetic and environmental factors, including the gut microbial community. These interactions between diet, genetics, and the microbiome present a significant challenge in the analysis of human disease.