Genetic and environmental control of host-gut microbiota interactions

Elin Org, Brian W. Parks, Jong Wha J. Joo, Benjamin Emert, William Schwartzman, Eun Yong Kang, Margarete Mehrabian, Calvin Pan, Rob Knight, Robert Gunsalus, Thomas A. Drake, Eleazar Eskin, Aldons J. Lusis

Research output: Contribution to journalArticlepeer-review

255 Scopus citations

Abstract

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 SNPbased 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.

Original languageEnglish
Pages (from-to)1558-1569
Number of pages12
JournalGenome Research
Volume25
Issue number10
DOIs
StatePublished - 1 Oct 2015

Fingerprint

Dive into the research topics of 'Genetic and environmental control of host-gut microbiota interactions'. Together they form a unique fingerprint.

Cite this