妊娠早期收缩压和舒张压升高与肠道微生物群和丁酸盐有关
Gomez-Arango et al. Hypertension (2016)
DOI 10.1161/HYPERTENSIONAHA.116.07910
妊娠早期收缩压和舒张压升高与肠道微生物群和丁酸盐有关
Increased Systolic and Diastolic Blood Pressure Is Associated withAltered Gut Microbiota Composition and Butyrate Production in Early Pregnancy
Abstract
The risk of developing pregnancy-inducedhypertension and preeclampsia is higher in obese pregnant women. In obesity,the composition of the gut microbiota is altered. Obesity is also associatedwith low-grade inflammation. Metabolites from the gut microbiota may contributeto both hypertension and inflammation. The aim of this study is to investigatewhether the composition of the gut microbiota in overweight and obese pregnantwomen is associated with blood pressure and levels of plasminogen activatorinhibitor-1. The composition of the gut microbiota was determined with 16Sribosomal RNA sequencing in 205 women at 16 weeks gestation from the SPRINGstudy (the Study of Probiotics IN Gestational diabetes). Expression ofbutyrate-producing genes in the gut microbiota was assessed by real- timepolymerase chain reaction. Plasminogen activator inhibitor-1 levels weremeasured in fasting serum of a subset of 70 women. Blood pressure was slightlybut significantly higher in obese compared with overweight women. The abundanceof the butyrate-producing genus Odoribacterwas inversely correlated with systolic blood pressure. Butyrate productioncapacity was decreased, but plasminogen activator inhibitor-1 concentrationsincreased in obese pregnant women. Plasminogen activator inhibitor-1 levelswere inversely correlated with expression of butyrate kinase and Odoribacter abundance. This study showsthat in overweight and obese pregnant women at 16 weeks gestation, theabundance of butyrate-producing bacteria and butyrate production in the gutmicrobiota is significantly negatively associated with blood pressure and withplasminogen activator inhibitor-1 levels. Increasing butyrate-producingcapacity may contribute to maintenance of normal blood pressure in obesepregnant women.
肠道微生物群可能通过多种机制影响宿主血压。链球菌、大肠杆菌、乳酸菌、双歧杆菌属细菌可在自主神经系统内合成神经递质。这些细菌丰度的变化可能会改变血管张力并导致高血压的发生。肠道微生物群影响宿主炎症反应，改变内皮功能，从而影响宿主血压。由于短链脂肪酸对血管张力的影响，肠道菌群产生的短链脂肪酸与高血压有关。本研究探讨了超重和肥胖孕妇肠道微生物群的组成与血压和纤溶酶原激活物抑制剂-1水平的相关性。
研究对象：205名超重和肥胖孕妇。
入组条件：参加SPRING研究的超重和肥胖孕妇，小于孕16周。
研究方法：采用16S rRNA基因V6-V8区测序，对205名受试者进行肠道微生物组成测定；采用qPCR检测肠道微生物区产丁酸基因的表达；选取70例受试者（28例超重孕妇和42例肥胖孕妇）检测空腹血清中纤溶酶原激活物抑制剂-1（PAI-1）的水平。
研究结论：
肥胖妇女的血压明显高于超重妇女；
产丁酸杆菌属的丰度与收缩压呈负相关。肥胖孕妇丁酸酯产生能力下降，纤溶酶原激活物抑制物-1浓度升高。
纤溶酶原激活物抑制物-1水平与丁酸激酶表达和丁酸杆菌属丰度呈负相关。
在孕16周超重和肥胖孕妇的肠道微生物群中，丁酸盐生产菌臭杆菌（Odoribacter）、梭菌（Clostridiaceae）的丰度和Buk基因的表达与收缩压呈负相关。臭杆菌（Odoribacter）丰度和Buk表达与炎症标志物pai1呈负相关，而PAI-1本身与血压呈正相关。
丁酸盐生产菌可能通过产生短链脂肪酸或影响炎症和PAI-1来改变宿主血压。
臭杆菌（Odoribacter）与血压和新陈代谢之间的关系表明，该物种也许可以作为益生菌改善宿主血压。
补充知识点：
SPRING研究：Study ofProbiotics IN Gestational diabetes，益生菌预防超重和肥胖妇女妊娠期糖尿病的多中心随机临床试验
[参考文献：Nitert MD, Barrett H, Foxcroft K, etal. (2013) SPRING: an RCT study of probiotics in the prevention of gestationaldiabetes mellitus in overweight and obese women. BMC Pregnancy Childbirth 13,50.]
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