Responsiveness of cardiometabolic-related microbiota to diet is influenced by host genetics

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.

Akkermansia muciniphilaand improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology

“…The observed differences in abundance of A. muciniphila into faeces may be due to actual changes in bacterial numbers, or alterations of the mucosal layer and gut architecture. Host genetics may also play a role in how dietary interventions influence gut microbiota and metabolic health, as previously shown in mice, where different strains had notably different gut microbial composition and intestinal environment that correlated with a variety of cardiometabolic profiles 63. The host's innate and adaptive immune system may also influence the composition of gut microbiota 64.…”

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

“…Inbred strain surveys in mice also demonstrate a significant effect of host genetic makeup on microbial diversity, 241 and some of these differences have been linked to cardiometabolic phenotypes. 242 However, the relative strength of environmental versus genetic signals on microbial regulation is unclear. Much of our knowledge of the environmental effects on the microbiome has been derived from studies in mice.…”

“…253 Bacterial species harboring putative choline utilization gene clusters (cut-c) have been suggested to play a central role in enteric trimethylamine formation 261 (and therefore downstream TMAO production). The specific microbiota capable of generating trimethylamine have not been fully identified, but previous reports have indicated a relationship between plasma TMAO and members of the Tenericutes phylum, 242,253 whereas species within the Desulfovibrio genus have also been demonstrated to degrade choline to trimethylamine. 261 Despite the compelling evidence of the microbiome as a critical mediator of CVD risk, we still do not understand the factors responsible.…”

Cumulative Environmental Impacts: Science and Policy to Protect Communities

“…These models offer information about gene-environment interactions, susceptibility, and the impact of individual or combined stressors on response. For example, diverse mice have illuminated genetic susceptibility to micronuclei formation for benzene, liver toxicity for trichloroethylene, and diet on intestinal cardiometabolic-related microflora (21,45,74). Co-exposures to arsenic and trichloroethylene have also been conducted (2).…”