Abstract
Intestinal microbial community structure is driven by host genetics in addition to environmental factors such as diet. In comparison with environmental influences, the effect of host genetics on intestinal microbiota, and how host-driven differences alter host metabolism is unclear. Additionally, the interaction between host genetics and diet, and the impact on the intestinal microbiome and possible down-stream effect on host metabolism is not fully understood, but represents another aspects of inter-individual variation in disease risk. The objectives of this study were to investigate how diet and genetic background shape microbial communities, and how these diet- and genetic-driven microbial differences relate to cardiometabolic phenotypes. To determine these effects, we used the 8 progenitor strains of the collaborative cross/diversity outbred mapping panels (C57BL/6J, A/J, NOD/ShiLtJ, NZO/HILtJ, WSB/EiJ, CAST/EiJ, PWK/PhJ, and 129S1/SvImJ). 16s rRNA profiling of enteric microbial communities in addition to the assessment of phenotypes central to cardiometabolic health was conducted under baseline nutritional conditions and in response to diets varying in atherogenic nutrient (fat, cholesterol, cholic acid) composition. These studies revealed strain-driven differences in enteric microbial communities which were retained with dietary intervention. Diet–strain interactions were seen for a core group of cardiometabolic-related microbial taxa. In conclusion, these studies highlight diet and genetically regulated cardiometabolic-related microbial taxa. Furthermore, we demonstrate the progenitor model is useful for nutrigenomic-based studies and screens seeking to investigate the interaction between genetic background and the phenotypic and microbial response to diet.Electronic supplementary materialThe online version of this article (doi:10.1007/s00335-014-9540-0) contains supplementary material, which is available to authorized users.
Highlights
The intestinal microbiome is associated with susceptibility to and development of several chronic metabolic diseases including diabetes (Larsen et al 2010), obesity (Turnbaugh et al 2008), and cardiovascular disease (Karlsson et al 2012)
We use a segregating panel of inbred mouse strains, representing *90 % of the genetic variation in mice (Roberts et al 2007), to examine the effects of genetics on intestinal microbiota and cardiometabolic risk factor response to diet
There are five main findings of our current studies: (1) differences in enteric microbial communities between inbred mouse strains are evident; (2) some of these strain-driven differences are retained and become more pronounced with dietary intervention; (3) microbial and phenotypic response to diet varies by mouse strain; (4) differences between the mouse strains suggest underlying differences in intestinal barrier function, inflammatory environment, short chain fatty acid (SCFA) production, and bile acid metabolism; and (5) the observed differences in a core group of microbial taxa are significantly related to cardiometabolic phenotypes
Summary
The intestinal microbiome is associated with susceptibility to and development of several chronic metabolic diseases including diabetes (Larsen et al 2010), obesity (Turnbaugh et al 2008), and cardiovascular disease (Karlsson et al 2012). Considering the interindividual variability at the level of the microbiome (Eckburg et al 2005; Qin et al 2010), detailed studies integrating the intestinal microbiome with disease risk complements current genome wide association studies and other efforts seeking to understand heterogeneity in health and disease status. Among others (Kaput 2008; PerezMartinez et al 2013) recognize that a ‘one size fits all’ approach to optimal nutritional and health status is not addressing the current epidemics of obesity, cardiovascular disease, and diabetes. Research models which simultaneously permit both dietary- and genetic-driven perturbations are an essential step in developing personalized approaches to nutrition and medicine
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