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Gut Microbiotal Dysbiosis and Increased Risk for Complex Polygenic Diseases Emerge with Genomic Selection for Low Aerobic Exercise Capacity
Author(s) -
Zhang Youjie,
Mell Blair,
Kumarasamy Sivarajan,
Cheng Xi,
Britton Steven L.,
Koch Lauren G.,
Joe Bina
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.884.2
Subject(s) - biology , genetics , genome , inbred strain , aerobic capacity , host (biology) , disease , inbreeding , microbiome , aerobic exercise , selection (genetic algorithm) , gene , medicine , population , endocrinology , environmental health , pathology , artificial intelligence , computer science , physical therapy
Bi‐directional host‐microbiotal interactions are increasingly being recognized as important factors contributing to the pathophysiology of complex polygenic diseases. While host genomes are inherited, the microbiome is acquired as a result of the composition of the microbiota that choose to reside within the host. The identities of the factors that determine which microbes choose to reside in a given host are unknown. Given the evidence for host‐microbiotal interactions in health and disease, we hypothesized that host genomes exert a selection pressure to influence the types of microbiota that reside in the host and that the resultant microbiotal composition is a pivotal determinant of the divide between health and disease of the host. To test this hypothesis, we developed models of health and disease by inbreeding rats divergent in aerobic exercise capacity. These novel inbred strains were developed by >20 generations of brother‐sister mating of the selectively‐bred low aerobic capacity rats and high aerobic capacity rats and named as LCR/BJ and HCR/BJ, respectively. Inbred HCR/BJ rats had significantly higher aerobic exercise capacity than inbred LCR/BJ rats as recorded by their total running distance to exhaustion of 1151 m vs. 130 m, respectively, p< 0.001. Next‐generation sequencing of the whole genomes of inbred HCR/BJ and LCR/BJ rats revealed considerable differences in their genomic sequences. To test whether this selection for differential genomic sequences resulted in any alterations in microbiota, fecal microbial communities of inbred LCR/BJ and HCR/BJ rats were profiled using 16S rRNA sequences. Interestingly, principal coordinates analysis displayed distinct clustering of the two cohorts (ANOSIM analysis, weighted UniFrac, P = 0.002), indicating significant phylogenetic differences of the microbial community structures between inbred LCR/BJ and HCR/BJ rats. Firmicutes/Bacteriodetes ratio was higher in the LCR/BJ rats compared with HCR/BJ rats suggesting the possibility of the increased risk for diseases in the LCR/BJ rats. Compared with inbred HCR/BJ rats, inbred LCR/BJ rats exhibited elevated blood pressure, increased body weight, lower circulating mean corpuscular hemoglobin, higher neutrophil‐to‐lymphocyte ratio, and higher immobility in the forced swim test. Metabolic phenotyping is currently underway. Overall, these studies provide clear evidence for the ability of the host genome to shape the microbiome and identify an inverse co‐evolutionary relationship between host genomic factors conferring enhanced aerobic exercise capacity and microbiotal dysbiosis driving disease risks.