Increased Systolic and Diastolic Blood Pressure Is Associated With Altered Gut Microbiota Composition and Butyrate Production in Early Pregnancy

Abstract

Abstract-The risk of developing pregnancy-induced hypertension and preeclampsia is higher in obese pregnant women.In obesity, the composition of the gut microbiota is altered. Obesity is also associated with low-grade inflammation.Metabolites from the gut microbiota may contribute to both hypertension and inflammation. The aim of this study is to investigate whether the composition of the gut microbiota in overweight and obese pregnant women is associated with blood pressure and levels of plasminogen activator inhibitor-1. The composition of the gut microbiota was determined with 16S ribosomal RNA sequencing in 205 women at 16 weeks gestation from the SPRING study (the Study of Probiotics in Gestational Diabetes). Expression of butyrate-producing genes in the gut microbiota was assessed by realtime polymerase chain reaction. Plasminogen activator inhibitor-1 levels were measured in fasting serum of a subset of 70 women. Blood pressure was slightly but significantly higher in obese compared with overweight women. The abundance of the butyrate-producing genus Odoribacter was inversely correlated with systolic blood pressure. Butyrate production capacity was decreased, but plasminogen activator inhibitor-1 concentrations increased in obese pregnant women. Plasminogen activator inhibitor-1 levels were inversely correlated with expression of butyrate kinase and Odoribacter abundance. This study shows that in overweight and obese pregnant women at 16 weeks gestation, the abundance of butyrate-producing bacteria and butyrate production in the gut microbiota is significantly negatively associated with blood pressure and with plasminogen activator inhibitor-1 levels. Increasing butyrate-producing capacity may contribute to maintenance of normal blood pressure in obese pregnant women. Gomez-Arango et al Blood Pressure and Gut Microbiome Butyrate Production 975The SCFA butyrate is produced from dietary fiber by bacteria in the gastrointestinal lumen. There are 2 main enzymes catalyzing butyrate production: butyrate kinase (Buk) and butyryl-CoA:acetate CoA-transferase (But), which are often used as biomarkers for the detection of butyrate-producing bacteria.11 Buk catalyzes the formation of butyrate from butyryl-CoA, releasing ATP in the process. 12,13 But catalyzes the reaction of butyryl-CoA with exogenous acetate to form butyrate and acetyl-CoA.13,14 Some butyrate-producing bacteria only express But or Buk, whereas others express both. 12The main butyrate producers in the human gut belong to the Firmicutes phylum (Coprococci, Eubacterium, Roseburia, and Faecalibacterium genera), 14 but members of other phyla, especially Bacteroidetes (Odoribacter and Alistipes genera), often contribute to the overall butyrogenic pool. SCFAproducing bacteria may affect blood pressure by direct effects of SCFA on vasodilation or through plasminogen activator inhibitor-1 (PAI-1). n-Butyrate increases PAI-1 mRNA in cultured hepatocytes, 15 and SCFA enemas stimulate rectal microcirculation and PAI-1 after aortic graft surgery. 16 It is uncl...

Alterations of Urinary Microbiota in Type 2 Diabetes Mellitus with Hypertension and/or Hyperlipidemia

“…This finding is similar to the findings of a previous study that detected Rikenella in the ceca of diabetic mice with dyslipidemia (Harris et al, 2012). In addition, a recent study of intestinal microbiota revealed that the relative abundance of Odoribacter is negatively correlated with systolic BP (Gomez-Arango et al, 2016), which is somewhat similar to the findings in the present study, as the relative abundance of Odoribacter in the DM+HT+HLP cohort was negatively associated with diastolic BP. Moreover, Chen et al reported a positive correlation between Dorea and LDL-C in a rat model of hyperlipidemia (Chen D. et al, 2014), and Dorea was also positively associated with LDL-C in the DM+HT+HLP cohort in the present study.…”

The gut microbiota: An emerging risk factor for cardiovascular and cerebrovascular disease

“…Furthermore, acetate supplementation down-regulated the renin-angiotensin system. In support of the functional role of short chain fatty acids, a recent study demonstrated that overweight and obese pregnant women at 16 weeks of gestation showed a negative correlation between the abundance of butyrate-producing bacteria and butyrate production by the gut microbiota with blood pressure [68]. By analyzing angiotensin II-infused GF and CONV-R C57BL/6 mice, we could show that the presence of commensal microbiota augments leukocyte adhesion and infiltration of neutrophils and monocytes into the aortic vessel wall, resulting in increased production of reactive oxygen species in the vasculature [65].…”

Antihypertensive Effects of Probiotics

“…Yet, obese school girls with high BP show lower abundance of Bacteroidetes in their gut microbiota than normal-weight girls [12]. In addition, overweight and obese pregnant women at 16-week gestation, the abundance of butyrate-producing bacteria, and butyrate production in the gut microbiota are significantly negatively associated with BP and with plasminogen activator inhibitor-1 (PAI-1) levels [13]. In that study, the abundance of the butyrate-producing genus Odoribacter was inversely correlated with systolic BP.…”

“…The effects of oral supplementation with probiotics in nonobese SHR, an established model of genetic hypertension characterized by elevated BP, arterial remodeling, endothelial dysfunction, vascular inflammation, and dysregulation of the immune system, were also studied [13]. Two groups of treatments with probiotics with inmunomodulatory properties were used: (a) Lactobacillus fermentum CECT5716 or (b) L. coryniformis plus L. gasseri.…”