RT Journal
A1 Org, Elin
A1 Parks, Brian W W
A1 Joo, Jong Wha J
A1 Emert, Benjamin
A1 Schwartzman, William
A1 Kang, Eun Yong
A1 Mehrabian, Margarete
A1 Pan, Calvin
A1 Knight, Rob
A1 Gunsalus, Robert
A1 Drake, Thomas A
A1 Eskin, Eleazar
A1 Lusis, Aldons J.
T1 Genetic and environmental control of host-gut microbiota interactions
JF Genome Research 
JO Genome Research 
YR 2015 
FD August 10 
DO 10.1101/gr.194118.115 
SP gr.194118.115 
UL http://genome.cshlp.org/content/early/2015/08/10/gr.194118.115.abstract 
AB Genetics provides a potentially powerful approach to dissect host-gut microbiota interactions. Toward this end, we profiled gut microbiota using 16s rRNA gene sequencing in a panel of 110 diverse inbred strains of mice. This panel has previously been studied for a wide range of metabolic traits and can be used for high resolution association mapping. Using a SNP-based approach with a linear mixed model we estimated the heritability of microbiota composition. We conclude that in a controlled environment the genetic background accounts for a substantial fraction of abundance of most common microbiota. The mice were previously studied for response to a high fat, high sucrose diet, and we hypothesized that the dietary response was determined in part by gut microbiota composition. We tested this using a cross-fostering strategy in which a strain showing a modest response, SWR, was seeded with microbiota from a strain showing a strong response, AxB19. Consistent with a role of microbiota in dietary response, the cross-fostered SWR pups exhibited a significantly increased response in weight gain. To examine specific microbiota contributing to the response, we identified various genera whose abundance correlated with dietary response. Among these, we chose Akkermansia muciniphila, a common anaerobe previously associated with metabolic effects. When administered to strain AxB19 by gavage, the dietary response was significantly blunted for obesity, plasma lipids, and insulin resistance. In an effort to further understand host-microbiota interactions, we mapped loci controlling microbiota composition and prioritized candidate genes. Our publically available data provide a resource for future studies.