TY  - JOUR
A1  - Org, Elin
A1  - Parks, Brian 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
Y1  - 2015/10/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1558 
EP  - 1569 
DO  - 10.1101/gr.194118.115 
VL  - 25 
IS  - 10 
UR  - http://genome.cshlp.org/content/25/10/1558.abstract 
N2  - 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, A×B19. 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 A×B19 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 publicly available data provide a resource for future studies. 
ER  -