A Systems Genetic Study Of Microbiome And Related Diseases

In recent years,a large number of studies in the field of biomedicine have shown that gut microbes have a complex and close relationship with the host’s metabolism,physiological status,and health maintenance.As the “second genome” of animals,gut microbes are affected by environmental and host genetic as well as other host phenotypes.With the application of Genome-Wide Association Study(GWAS)in the field of gut microbes,more and more SNPs that regulate the diversity and abundance of microbes have been identified.However,it is still unclear how the host genetics affect the composition and the abundance of gut microbes.In addition,compared with healthy people,patients with diseases are often accompanied by a series changes of gut microbes,including gut microbes’ composition,function and microbe abundance.These changes are collectively referred to as “gut microflora disorders”.However,the relationship between “gut microflora disorder” and disease has yet to be determined.Based on the GWAS summary data of 22 gut microorganisms,our study investigated the problems that how the host genetics affect the abundance of gut microbes and what is the relationship between gut microbes and disease.Firstly,we used the GWAS summary data of gut microbes and pathway data from multiple databases such as Reactome,KEGG,Wikipathway and GO.Based on GSAE(Gene Set Enrichment Analysis),we identified the signaling pathways involved in host genetic regulation of gut microbial abundance.Subsequently,we used the identified SNPs that are only significantly related to vitamins and mineral nutrition to analysis the casual relationship between gut microbes change and vitamins/ mineral nutrition.Three mendelian randomization method were used in this study.The results show that the concentration changes of vitamin D are responsible for the abundance change of the Erysipelotrichia,Erysipelotrichales,and Erysipelotrichaceae.The increase of calcium concentration will increase the abundance of Actinobacteria and Actinobacteria.And the concentration increase of iron and zinc will reduce the anbundance of Bacilli,Lactobacillales and Marinilabiliaceae.In order to identify the relationship between the abundance change of gut microbial and disease,we obtained the GWAS summary data of 22 gut microbe and the information of gene-disease relationship from Dis Ge Net database.The GSEA method based on GWAS summary data and the Hot Net2 method were used to identify the association between gut microbes and complex diseases.In this study,a total of 48 pairs of associations between 20 gut microorganisms and 21 diseases were identified,and 56.25%(27/48)of the associations between gut microbes and diseases were supported by relevant research.Subsequently,the Mendelian randomization method was used to analyze the causal relationship between the above 48 gut microbe-disease pairs.However,we did not find a causal relationship between the gut microbes and diseases.These results suggest that the relationship between gut microbes and diseases may be complicated,and may not be defined as simple causal relationship.In practice,it needs further research in the use of gut microbes as targets for disease treatment.In summary,we used systematic genetics methods to study the relationship between vitamin/ mineral nutrition and gut microbes,and the relationship between diseases and intestinal microbes.We found that some vitamin/ mineral nutrition will regulate gut microbes.However,non-causal relationship between gut microbes and disease was observed.These results laid a preliminary theoretical for the in-depth study of the genetic mechanism of gut microbes and their relationship with diseases.