High-salt-diet-induced Gut Microbiota Contributes To The Development Of Hypertension

Background and objectiveHypertension is a disease with high prevalence,low prevention rate and numerous complications,which causes a heavy burden on the country and families.However,as the precise pathogenesis of hypertension has not yet been elucidated,the prevention and long-term control of hypertension are not ideal.High salt diet is one of the most important risk factor for hypertension and it has been proven to induce hypertension through multiple pathways.It has been studied that high salt diet could impact the composition of gut microbiota in mice,and the change in gut microbiota may contribute to the development of hypertension.Yet,the study about the influence of high salt diet on gut microbiota in human is still lacking.Hence,the aim of this study is to investigate the influence of high salt diet on gut microbiota in human and trying to figure out the relation between high salt diet,gut microbiota and development of hypertension through animal experiment.MethodsThe 1st experiment:Select population from 14 districts of Guangdong province by PPS sampling method,collecting background data including age,sex,dietary condition and BMI and so on from 2615 participants,and attaining gut microbiota data via Illumina high-throughput sequencing.Participants were grouped into low sodium diet group(LSD),mid sodium diet group(MSD)and high sodium diet group(HSD)based on the sodium intake,analyzing the relation between gut microbiota and sodium intake.The 2nd experiment:40 C57BL/6J male mice were divided into normal diet group(ND),normal diet and Klebsiella group(ND+Kleb),high salt diet group(HSD),high salt diet and Klebsiella group(HSD+Kleb)randomly.Intervention were given to mice according to different group.During intervention,blood pressure date and stool samples of mice were collected.At the end of the experiment,mice were sacrificed and several tissue samples were collected for assays.Results1.The high salt diet did not affect the alpha diversity of the gut microbiota,but the composition of gut microbiota were affected to some extent.At the genus level,there were nine genera enriched in HSD group,including Klebsiella,Bulleidia and Enhydrobacter,and nine genera decreased in HSD group,including Dialister,Psychrobacter and Anaerostipes.At the sequence level,51 strains of differential bacteria were found and correlation analysis was performed between the differential bacteria and sodium intake.After corrections with age,gender,stool score and so on though MaAsLin,we found that Dialister,Seq9431,Bacteroides ovatus.Seq12167 and Lachnospiraceae.Seq5551 were inversely correlated with sodium intake and Faecalibacterium_prausnitzii.Seq14927,Klebsiella.Seq1787 and Bulleidia moorei.Seq3125 were positively correlated with sodium intake.Further more,we found that Klebsiella.Seq1787 was the only bacterium positively correlated with sodium intake after correction with dietary pattern.2.The signal of Klebsiella and blood pressure were elevated in the mice with high salt diet and intervention of Klebsiella.The high-salt diet increased the pH of gastric acid in mice.Colonization of Klebsiella resulted in an increase in the number of Th17 cells within the mesenteric lymph node and spleen.ConclusionsThe high-salt diet led to the enrichment of Klebsiella in the gut microbiota of population.And mice experiment have found that the high-salt diet could promote the colonization of Klebsiella in the gut microbiota,which might correlate with the increase of pH of gastric acid.The colonization of Klebsiella could increase the number of Th17 cells within the mesenteric lymph node and spleen and lead to increased blood pressure.