Restructuring the Gut Microbiota by Intermittent Fasting Lowers Blood Pressure

Authors

Huanan Shi
Bojun Zhang
Taylor Abo-Hamzy
James W Nelson
Chandra Shekar R Ambati
Joseph F Petrosino
Robert M Bryan
David J Durgan

Publication Date

4-30-2021

Journal

Circulation Research

DOI

10.1161/CIRCRESAHA.120.318155

PMID

33596669

PMCID

PMC8085162

PubMedCentral® Posted Date

4-30-2022

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Animals, Bile Acids and Salts, Cecum, Cholic Acid, Dysbiosis, Fasting, Gastrointestinal Microbiome, Germ-Free Life, Hypotension, Metabolome, Oleanolic Acid, Random Allocation, Rats, Rats, Inbred SHR, Rats, Inbred WKY, Receptors, G-Protein-Coupled, Specific Pathogen-Free Organisms, Time Factors, Whole Genome Sequencing, microbiota, dysbiosis, metabolomics, bile acids, intermittent fasting, Hypertension, Diet and nutrition, Physiology, Animal models of human disease, Basic science research

Abstract

Rationale:

In recent years, it has been demonstrated that a pathological change in the gut microbiota, termed gut dysbiosis, can be an underlying factor for the development of hypertension. Prevention of this dysbiosis can attenuate or abolish hypertension. Translational mechanisms to prevent gut dysbiosis as well as understanding of the mechanisms linking gut dysbiosis to hypertension are lacking.

Objective:

We first examined the efficacy of intermittent fasting (IF) in altering the gut microbiota and lowering blood pressure (BP). Next, we utilized a multi-omics approach to examine microbial influenced metabolites that may serve as the link between the gut microbiota and host BP regulation.

Methods and Results:

We demonstrate that IF significantly altered the makeup of the gut microbiota, cecal and plasma metabolome, and prevented the development of hypertension in the spontaneously hypertensive stroke-prone rat (SHRSP). The beneficial effects of IF were shown to be due to alterations of the gut microbiota through germ-free (GF) transplantation studies. GF rats receiving microbiota from IF SHRSP had significantly lower BP as compared to GF rats receiving microbiota from ad libitum fed SHRSPs. Through whole genome shotgun sequence analysis of the microbiota and untargeted metabolomics of cecal content and plasma we identified bile acid (BA) metabolism as a potential mediator in BP regulation. Finally, we show supplementation with cholic acid, or activation of the G protein-coupled BA receptor (TGR5), significantly reduced BP of the SHRSP.

Conclusions:

These studies demonstrate the BP lowering effects of IF involves manipulation of the gut microbiota and metabolome, and implicates disrupted BA signaling as novel mechanisms by which gut dysbiosis contributes to hypertension.

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