Abstract

Food-derived oligosaccharides show promising therapeutic potential in lowering blood pressure (BP), but the mechanism is poorly understood. Recently, the potential role of gut microbiota (GM) in hypertension has been investigated, but the specific GM signature that may participate in hypertension remains unclear. To test the potassium alginate oligosaccharides (PAO) mechanism in lowering BP and specific microbial signature changes in altering GM, we administered various dosages of PAO in 40 spontaneously hypertensive rats for a duration of six weeks. We analyzed BP, sequenced the 16S ribosomal DNA gene in the cecum content, and gathered RNA-seq data in cardiac tissues. We showed that the oral administration of PAO could significantly decrease systolic BP and mean arterial pressure. Transcriptome analyses demonstrated that the protective effects of developing heart failure were accompanied by down-regulating of the Natriuretic Peptide A gene expression and by decreasing the concentrations of angiotensin II and atrial natriuretic peptide in plasma. In comparison to the Vehicle control, PAO could increase the microbial diversity by altering the composition of GM. PAO could also decrease the ratio of Firmicutes to Bacteroidetes by decreasing the abundance of Prevotella and Phascolarctobacterium bacteria. The favorable effect of PAO may be added to the positive influence of the abundance of major metabolites produced by Gram-negative bacteria in GM. We suggest that PAO caused changes in GM, and thus, they played an important role in preventing the development of cardiovascular disease.

Highlights

  • Hypertension (HTN) has been identified as the leading cause of mortality and disability worldwide because of the high frequency and concomitant risks of cardiovascular diseases (CVD), including stroke and heart failure (HF) [1,2,3]

  • In our previous study based on our data of the 16S ribosomal DNA gene sequencing, we found out that alginate oligosaccharides altered the microbiota composition and decreased the ratio of Firmicutes and Bacteroidetes in pig fecal bacteria [26]

  • The abundance of Coriobacteriaceae was reported to show a significant increase in hypertensive rats fed on the high-fat diet [39]; the abundance was higher in the Vehicletreated group (Vehicle)-treated group compared to those in the HPAO, LPAO, and Captopril groups

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Summary

Introduction

Hypertension (HTN) has been identified as the leading cause of mortality and disability worldwide because of the high frequency and concomitant risks of cardiovascular diseases (CVD), including stroke and heart failure (HF) [1,2,3]. Alginate oligosaccharides are indigestive in the small intestine but fermented in the colon, where they are colonized by commensal bacteria, which are known as gut microbiota (GM) [9]. Hidalgo et al suggested that an extra virgin olive oil-enriched diet reduced HTN-related profile changes of GM in spontaneously hypertensive rats (SHR) [19]. The specific microbial signature associated with HTN and the mechanism lowering BP need to be revealed after interventions with alginate oligosaccharides.

HPAO and LPAO Decreased BP in SHR
HPAO Interventions Attenuated Cardiac Fibrosis
Cardiac Transcriptome
PAO Altered Gut Microbiota Dysbiosis in SHR
Discussion
Preparation of PAO
Animal Model and Treatment
Gut Microbiome
Analyses of SCFAs
Histological Analyses
RNA Extraction and Cardiac Transcriptome Sequencing
Bioinformatic Analyses
Real-Time Quantitative PCR Analyses
Statistical Analysis
Conclusions
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