Understanding The Effects Of Host Genetics On Gut Microbiota Composition And Gut Microbiota On Blood Glucose And Lipid Traits In Pigs

Mamualain gastrointestinal tract harbors a complex microbial community that keeps close interaction with host and exert profound effects on host metabolic phenotypes.However,the interactions between gut microbiome,host genetics and metabolic phenotypes are still unclear.In the current paper,the studies were performed in Chinese Erhualian pigs and Bamaxiang pigs to investigate the host genetic effect on the composition of instestinal microbiota using the cecum luman and feces samples from these two pig populations.We also evaluated the effects of gut microbiota on host serum glucose and blood lipids with the cecum lumen samples from Erhualian pigs.The major results are present as follows:1.The comparison of the similarity of gut microbial composition among full-sibs,half-sibs and unrelated members showed a higher similarly of beta-diversity between sib members than unrelated members.The correlation analysis between host genetic kinship and the microbiome-based relationship also confirmed the effect of host genetics on microbiota composition in both pig population.In the heritability estimation,we identified 81 and 67 microbial taxa having h2 > 0.15 in the fecal and cecum luminal samples,respectively,including 31 taxa with h2 > 0.15 in both types of samples.Moreover,our GWAS identified 40 and 34 significant associations.A total of 71 candidate genes that were related to the abundance or presence/absence of bacterial taxa were isolated from these loci in both types of samples.We found that the functional classification of host candidate genes for microbial taxa are mainly associated with metabolisms,immunity functions and signal transduction.The high similarity of heritable taxa and functional categories of candidate genes among pig,human and mouse suggests the conservation of the host genetic effect on gut microbiome across species.The results from this study provided another evidence that host genetics contributes significantly to the gut microbiome.2.In the association study between blood glucose and lipid parameters,and gut bacteria in Erhualian pigs,we identified dozens of bacterial species related to blood glucose and blood lipids.We found that bacteria that produce short-chain fatty acids,especially butyric acid-producing bacteria,such as Coprococcus,Roseburia,Lachnospiraceae and Faecalibacterium were associated with fasting glucose.We also found that inflammatory-related bacteria from Proteobacteria and Clostridium are related to increased levels of total cholesterol(TC),low-density lipoprotein cholesterol(LDL),ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol(LDL/HDL),atherosclerosis index(AI).We further found some potential bacteria related to decreased blood lipids levels,such as Lactobacillus and Bacilli.In the analysis of the relationships between metagenomic function,and blood glucose and lipids,we found that the KEGG functional pathways involved in nutrient uptake,transport and carbohydrate metabolism are related to blood glucose,while functional pathways related to antioxidant metabolism and bile acid secretion were significantly associated with blood lipids.In addition,through a 100-fold cross-validation analysis,we found that the gut microbiota accounts for 23.8% of the phenotypic variation of blood glucose and 5.95%,6.02%,4.12%,6.56% phenotypic variation of TC,LDL,LDL/HDL and AI,while only explained 1.69% in phenotypic variation of HDL.Our results suggested that host genetics have significant effect on the composition of gut microbiota.Genes associated with gut flora are mainly related to immunity,metabolism and signal transduction.Our research also suggested that the interaction between gut microbiota and host genetics were conserved in different mammals.In addition,our results also indicated that intestinal flora should affect blood glucose and lipid levels through the short-chain fatty acids(SCFAs)and their involvement in bile acid metabolism pathways.the results from this study provides important information for the effect of host genetics and gut microbiota and provided basic knowledge for the further study of gut flora influencing the metabolic phenotype.