Association Of Hypertension With Intestinal Flora And Metabolites In Han,Bai And Yi Ethnic Groups In Yunnan

Objective:Based on the association of gut microbiota and serum metabolites with hypertension in different ethnic groups,16 s high-throughput sequencing and metabolomics analysis were used to compare the differences in gut microbiota and metabolites among Han,Bai and Yi hypertensive ethnic groups in Yunnan.To screen the characteristic flora and differential metabolites that mediate the development of hypertension in different ethnic groups in Yunnan,and to analyze their correlation,to explain their role in mediating the development of hypertension in different ethnic groups,and to further explore the possible mechanism of hypertension in different ethnic groups in Yunnan Methods:This study was based on the field baseline survey of the China Multi-Ethnic Cohort(CMEC)in Yunnan province,which had been established by the key special project of Precision Medicine of the National Key Research and Development Program.A cohort study was conducted in Han hypertensive ethnic groups from Yongsheng County of Lijiang,Bai hypertensive ethnic groups from Heqing County of Dali,and Yi hypertensive ethnic groups from Yongren County of Chuxiong,Yunnan Province.According to the international definition of hypertension,the subjects were divided into Han,Bai and Yi groups.After collecting their serum and fecal samples strictly according to the inclusion and exclusion criteria of the study,the fecal samples of 30 Han people,20 Bai people and 16 Yi people were finally selected for 16 S rRNA high-throughput sequencing,and the serum samples of the same people were subjected to untargeted metabolomics analysis.Based on 16 S rRNA high-throughput sequencing and metabolomics,we analyzed the structural changes of intestinal flora and the differences in metabolites among the three different ethnic groups,and further explored the key strains and key metabolites affecting the occurrence of hypertension in different ethnic groups.Combined with the above analysis,we correlated with the basic information of the baseline survey population.To explore the possible influencing factors and mechanisms of gut microbiota and metabolites in mediating the development of hypertension in different ethnic groups.Results:1.Analysis of the basic characteristics of the population: A total of 10201 Han ethnic groups were investigated,including 3052 hypertension patients,with a prevalence of 29.91%;A total of 6310 Bai people were investigated,among which2299 were hypertension patients,with a prevalence rate of 36.4%.A total of 6147 people of Yi nationality were investigated,among which 2353 were hypertension patients,with a prevalence rate of 38.3%.There is a statistically significant difference in the prevalence of hypertension between Han and Bai,Bai and Yi,Han and Yi.(P<0.001,P=0.033,P <0.001).2.The results of intestinal flora diversity showed that compared with Yi and Bai groups,the richness and diversity of intestinal flora in Han group were lower(P<0.05).Compared with Bai and Han hypertension groups,the number of intestinal flora species in the hypertension group of Yi is relatively higher,and there are more unique intestinal flora species.In this study,it was found that Bacteroideta was the highest in the Bai group,followed by the Han group and the lowest in the Yi group,and the difference was statistically significant(P<0.05).Patescibacteria has the highest relative abundance in Han group,followed by Bai group and Yi group,with statistical significance(P<0.05).The relative abundance of Blautia was highest in Han ethnic group,followed by Yi ethnic group and lowest in Bai ethnic group,and the difference was statistically significant(P<0.05).The relative abundance of Clostridium＿sensu＿stricto＿1 beneficial bacteria was the highest in Bai ethnic group,followed by Yi and lowest in Han,and the difference was statistically significant(P<0.05).3.Metabolomics analysis showed that the number of differential metabolites between the Han and Bai groups was the largest,which was 208.The Han and Yi ethnic groups had the least differential metabolites is 100.The number of differential metabolites between Yi and Bai ethnic groups was in the middle,which was 192.There were 7 important differential metabolites between Han and Bai:13-Hydroxy-9-methoxy-10-oxo-11-octadecenoic acid Methyl cellulose,PE(18:4(6Z,9Z,12 Z,15Z)/20:5(5Z,8Z,11 Z,14Z,17Z)),Acetylpterosin C,Beta-Solamarine,Permetin A and DG(15:0/14:1(9Z)/0:0).Five important differential metabolites were identified between Han and Yi: Furohyperforin,MG(0:0/24:1(15Z)/0:0),Triptohypol F,PE(P-16:0e/0:0)and Acetylpterosin C.Six important differential metabolites between Bai and Yi,10,20-dihydroxyeicosanoic acid,13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid,Phenylalanyl-Tryptophan,5-Nonyltetrahydro-2-oxo-3-furancarboxylic acid,Benzoquinoneacetic acid,and2-Hydroxy-3-methoxyestrone.Bai and yi group differences metabolites Phenylalanyl-Tryptophan,Phenylalanylphenylalanine,Lyso PE(0-0 draw/then(6 z,z,z))was generally lower trend,such as the bai group generally increase trend.In addition,Blumealactone A,Cyclocalopin C1,Osmaronin and 4’-Dihydroabscisic acid contributed most to the differential metabolites between Yi and Bai ethnic groups.The differential metabolites 20-Hydroxy-PGF2 a,Tyrosyl-Isoleucine,Isoleucyl-Tyrosine,Leu Gln Lys Ser Leu were upregulated in Bai but downregulated in Han.P-Hydroxyphenylbutazone,Acetylpterosin C,and13-Hydroxy-9-methoxy-10-oxo-11-octadecenoic contributed most to the differential metabolites between the Han and Bai groups acid and{[(2E)-3-phenylprop-2-en-1-yl]oxy}sulfonic acid.3-Indoleacetic was the differential metabolite between the Han and Yi groups acid,PE(P-16:0e/0:0),15-Oxo EDE,(+/-)12(13)-Epome,(13R,14R)-7-labdene-13,14,15-triol were up-regulated in Yi population.Blumealactone A,Glu Tyr Lys,Lepidiumterpenyl ester,etc.showed a downward trend.In addition,Blumealactone A,P-Hydroxyphenylbutazone,Acetylpterosin C and Norstictic acid contributed more to the metabolic differences between Han and Yi.There were 9 significantly enriched differential metabolic pathways between Han and Bai groups,mainly arginine biosynthesis,phospholipid metabolism,and caffeine metabolism pathways.A total of 32 differentially expressed metabolic pathways were significantly enriched between Han and Yi ethnic groups,among which linoleic acid metabolism,alanine,aspartate and glutamate metabolism pathways were more important.A total of 12 differentially expressed metabolic pathways were significantly enriched between Bai and Yi ethnic groups,mainly including linoleic acid metabolism,alanine,aspartate and glutamate metabolism and arginine biosynthesis.The characteristic flora Blautia of Han ethnic group was positively correlated with UREA(r>0,P<0.05).The characteristic Clostridium＿sensu＿stricto＿1 of Bai ethnic group was negatively correlated with TG and GGT(r<0,P<0.05),and positively correlated with LDL(r>0,P<0.05).Virgibacillus was negatively correlated with ALB(r<0,P<0.01).Conclusions:1.The prevalence of hypertension was 29.91%,36.4% and 38.3% in Han,Bai and Yi ethnic groups,respectively.There were significant differences in the prevalence of hypertension among the three ethnic groups.2.There are differences in intestinal flora among the hypertensive population of Han Bai and Yi ethnic groups living in Yunnan.The intestinal community structure of the hypertensive population is changed,and the diversity and richness of microflora are lower than that of the normal population.The relative abundance of Blautia was the highest in Han ethnic groups.The Clostridium＿sensu＿stricto＿1 relative abundance is the highest among the Bai ethnic group.The increase of the abundance of Bacteroides and Virgibacillus in Yi ethnic group may increase the level of inflammation,which may be involved in the occurrence and development of hypertension in Yi ethnic group.3.Three fatty acids,one terpenoid,one indole,one carbohydrate and one new polypeptide antibiotic were found to play important roles in the differential metabolites between Han and Bai ethnic groups.Two terpenoids,two fatty acids and one indole were found in the differential metabolites between Han and Yi ethnic groups.Four fatty acids,one amino acid and one steroid were found in the differential metabolites between Bai and Yi ethnic groups.The differential metabolites among different ethnic groups were mainly enriched in linoleic acid metabolism,phospholipid metabolism and alanine,aspartate and glutamate metabolism pathways.4.The intestinal characteristic flora of hypertensive people of different ethnic groups may be related to liver-related metabolism.The abnormal flora of hypertensive people of Yi ethnic group is associated with the disorder of liver metabolism or function impairment,while the characteristic flora of Bai ethnic group is associated with liver lipid metabolism and liver injury.