Genetic and environmental control of host-gut microbiota interactions

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.

Social Environment Has a Primary Influence on the Microbial and Odor Profiles of a Chemically Signaling Songbird

“…Among humans, despite high inter-individual variation in the composition and structure of gut microbiota, microbial community signatures are still generally evident at the level of family households and even nations (Turnbaugh et al, 2009;Lee et al, 2011;Yatsunenko et al, 2012;Goodrich et al, 2014). These patterns could be due to either variation in shared environments or genetic relatedness (Spor et al, 2011;Goodrich et al, 2014;Org et al, 2015). Most available data suggest a strong environmental component in shaping the human gut microbiota: cohabiting parents have more similar gut microbiota than do men and women not living together (Yatsunenko et al, 2012), and monozygotic and dizygotic twin pairs generally have gut microbiota that differ to similar degrees (Turnbaugh et al, 2009;Lee et al, 2011;Yatsunenko et al, 2012).…”

“…Nest-specific microbial and volatile odor profiles could reflect influences of shared environments and/or genetic relatedness, and teasing these influences apart is one of the most pressing lines of inquiry in host microbial ecology (Spor et al, 2011;Goodrich et al, 2014;Org et al, 2015). Dark-eyed juncos afford an opportunity to do so because they are socially monogamous yet exhibit appreciable levels of extra-pair paternity (Ketterson et al, 1998;Gerlach et al, 2012a,b;Atwell et al, 2014), and although they biparentally provision their offspring, only mothers brood the eggs and nestlings (Nolan et al, 2002).…”

“…For example, symbiotic microbes provide their hosts with access to otherwise inaccessible energy and nutrients (Tremaroli and Backhed, 2012;Hacquard et al, 2015), they prime and bolster host immune systems (Hooper et al, 2012;Lee and Hase, 2014), they catalyze the effective development and functioning of host organs (McFall-Ngai, 2002;Fraune and Bosch, 2010), and they can directly contribute to their hosts' behavioral phenotypes (Archie and Theis, 2011;Ezenwa et al, 2012), including chemical signals used in intraspecific communication (Archie and Theis, 2011;Ezenwa and Williams, 2014). A key line of inquiry in contemporary host-microbial ecology is determining the relative influence of the environment and host genotype on the development of an individual host's microbiota (Spor et al, 2011;Goodrich et al, 2014;Org et al, 2015). Teasing apart these effects is particularly intriguing when considering the potential contribution of symbiotic microbes to intraspecific chemical signaling because animals' chemical signals are often thought to be indicative of individual genetic quality (Johansson and Jones, 2007), particularly when they are related to immune function or parasite load (Penn and Potts, 1998).…”

Efficient and Accurate Multiple-Phenotype Regression Method for High Dimensional Data Considering Population Structure

“…The data set contains 6138 probes and 2956 genotyped loci in 112 segregants. In addition, we evaluated our method using a gut microbiome data set (Org et al 2015) collected from 592 mice representing 110 HMDP strains. The study protocol has been described in detail by Parks et al (2013).…”

“…Performing a multiple-phenotypes analysis with microbiome data may produce results that allow more complete reconstruction of these networks. We applied the standard ttest, EMMA (Kang et al 2008), MDMR (Zapala and Schork 2012), and GAMMA on a gut microbiome data set (Org et al 2015) from HMDP that contains 26 common genus-level taxa identified from 592 mice samples, including 197,885 SNPs.…”