| Objective: To Find evidence of gut microbiota and short-chain fatty acids(SCFA)associated with preeclampsia pathogenesis,which will provide new clinical perspectives for the treatment of preeclampsia(PE).Methods: We totally recruited 63 pregnancy women in third trimester,including 27 PE patients and 36 healthy pregnant women without complicated pregnancy from the Department of Obstetrics in Ren Ji Hospital(School of Medicine,Shanghai Jiao Tong University)from August 2017 to October 2018.Collecting about 5 g of fresh stool in the middle of the two subjects in a sterile dry tube to extract the DNA.We performed 16 Sr RNA sequencing and gas chromatography to compare the gut microbiota(GM)and fecal short chain fatty acids(SCFA)levels between two group.We used Phylogenetic reconstruction of unobserved states(PICRUSt)to predict the metabolic pathways that the GM may be involved in.Spearman correlation analysis between differential GM and SCFA were performed.Finally,on the 5th and 10 th day of pregnancy,Sprague-Dawley(SD)rats were given lipopolysaccharide(LPS)stimulation through the tail vein to establish pregnancy hypertension(PH)rat model,then we gave the butyrate from 4th till 19 th to treat the PH rats.Results: There was no significant difference in maternal age,gestational weeks at fecal samples collection,gravidity,parity,and body mass index(BMI)before pregnancy between the two groups.The PE group had more adverse perinatal outcomes such as induced premature birth < 35 weeks,fecal growth restriction,and perinatal death than the healthy pregnant control(HPC)group.Compared with the HPC group,patients with PE had significant decreased GM diversity and altered abundance(P < 0.001): Firmicutes(P < 0.05)and Blautia(P < 0.001),Eubacterium_rectale(P < 0.001),Eubacterium_hallii(P < 0.001),Streptococcus(P < 0.001),Bifidobacterium(P < 0.05),Alistipes(P < 0.01),Collinsella(P < 0.01),and Subdoligranulum(P < 0.05)decreased significantly in the PE group,while Proteobacteria(P < 0.001)and Escherichia_Shigella(P < 0.001),Enterobacter(P < 0.01)increased significantly in the PE group.We also use the PICRUSt analysis to predict the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways and found that the relative abundance of LPS synthesis pathway increased and G protein-couple receptors(GPCR)pathway decreased significantly in patients with PE.To be interested was the finding that increased relative abundance of LPS biosynthesis pathway and decreased relative abundance of GPCR pathways correlated highly with the differential GM that we found in patients with PE.Both the fecal butyric acid(P < 0.05)and valeric acid(P < 0.001)levels decreased significantly in the PE group.Valeric acid positively correlated with Firmicutes(P < 0.01)and Eubacterium_rectale,Eubacterium_hallii,Collinsella(P < 0.001),Alistipes,Blautia(P < 0.01),Streptococcus,and Subdoligranulum(P < 0.05),and negatively correlated with Proteobacteria(P < 0.01)and Enterobacter,Escherichia_Shigella(P < 0.01).Butyric acid positively correlated with Firmicutes(P < 0.01)and Eubacterium_rectale(P < 0.001),Eubacterium_hallii,Blautia,Subdoligranulum(P < 0.01),Collinsella(P <0.05),and negatively correlated with Proteobacteria(P < 0.01)and Escherichia_Shigella(P < 0.001).After successfully established LPS-induced rat model of PH,oral administration of butyrate can significantly reduce the blood pressure of those PH rats.Conclusions: The diversity and the relative abundance of GM changed in patients with PE.Through prediction function we found that the relative abundance of LPS synthesis pathway increased and GPCR pathway decreased significantly in patients with PE.Both of the fecal butyric acid and valeric acid decreased significantly in the PE group.Oral administration of butyric acid decreased significantly the blood pressure of LPS-induced rat model of PH in vivo.To sum up,the synergistic effects of GM dysbiosis and reduced SCFA may promote the development of hypertension in patients with PE. |
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