Antihypertensive effects of exercise involve reshaping of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rat

Gut Microbes. 2021 Jan-Dec;13(1):1-24. doi: 10.1080/19490976.2020.1854642.


Exercise (Ex) has long been recognized to produce beneficial effects on hypertension (HTN). This coupled with evidence of gut dysbiosis and an impaired gut-brain axis led us to hypothesize that reshaping of gut microbiota and improvement in impaired gut-brain axis would, in part, be associated with beneficial influence of exercise. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise for 12 weeks, whereas, detrained groups underwent 8 weeks of moderate-intensity exercise followed by 4 weeks of detraining. Fecal microbiota, gut pathology, intestinal inflammation, and permeability, brain microglia and neuroinflammation were analyzed. We observed that exercise training resulted in a persistent decrease in systolic blood pressure in the SHR. This was associated with increase in microbial α diversity, altered β diversity, and enrichment of beneficial bacterial genera. Furthermore, decrease in the number of activated microglia, neuroinflammation in the hypothalamic paraventricular nucleus, improved gut pathology, inflammation, and permeability were also observed in the SHR following exercise. Interestingly, short-term detraining did not abolish these exercise-mediated improvements. Finally, fecal microbiota transplantation from exercised SHR into sedentary SHR resulted in attenuated SBP and an improved gut-brain axis. These observations support our concept that an impaired gut-brain axis is linked to HTN and exercise ameliorates this impairment to induce antihypertensive effects.

Keywords: Exercise; gut-brain axis; hypertension; microbiota; microglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure
  • Brain-Gut Axis / physiology*
  • Cardiomegaly / prevention & control
  • Fecal Microbiota Transplantation
  • Gastrointestinal Microbiome / genetics
  • Gastrointestinal Microbiome / physiology*
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / pathology
  • Hypertension / pathology
  • Hypertension / therapy*
  • Inflammation / prevention & control
  • Male
  • Microglia / metabolism
  • Paraventricular Hypothalamic Nucleus / pathology
  • Permeability
  • Physical Conditioning, Animal / physiology*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Sympathetic Nervous System / pathology

Grants and funding

This study is supported by the National Natural Science Foundation of China (Nos. 81700373, 81770426, 81600333 and 81800373), the China Postdoctoral Science Foundation (grant numbers 2019M660259), the Ministry of education Chunhui plan project and the Basic Research Program of Natural Science in Shaanxi Province (2020JQ-085)..