Abstract

It is well established that hypertension is associated with autonomic dysfunction and gut dysbiosis. Here, we show that chronic inulin/FOS‐rich diet alters gut microbiota, promotes autonomic dysfunction, and increases BP in conscious unrestrained spontaneously hypertensive rat (SHR), as well as the SHR submitted to restraint stress. These alterations were accompanied by activation of cardioregulatory brain regions, namely the paraventricular nucleus (PVN) of hypothalamus and solitary tract nucleus (NTS), as measured by manganese‐enhanced magnetic resonance imaging (MEMRI). BP was also significantly increased in the inulin/FOS diet‐fed Wistar‐Kyoto (WKY) rat submitted to restraint stress, albeit to a lesser extent.MethodsMale 4 weeks old WKY and SHR were placed on either the inulin/fructooligosaccharides (FOS)‐rich diet (fiber, n=6), or its calorie‐matched control diet (ctl, n=6) (Research Diets, Inc.) for 14 weeks. BP was measured weekly by tail cuff and telemetry, and during 20 minutes of restraint stress. Spectral analysis of BP waveform signal was performed to derive autonomic variables. MEMRI was performed in SHR at tenth week on diet.ResultsInulin/FOS‐rich diet caused significant shifts in gut bacterial profiles in WKY and SHR as an increase in Bifidobacterium population (WKY: 0.006624 ± 0.0018 vs. 0.4989 ± 0.1745 arbitrary unit; p=0.0073, n=6. SHR: 0.03099 ± 0.0127 vs. 0.2134 ± 0.0656 arbitrary unit; p=0.0258, n=6). We observed no change in BP in conscious unrestrained WKY; however, conscious unrestrained SHR fed with inulin/FOS diet had significantly higher mean BP compared to control (163.8 ± 1.6 vs. 169.6 ± 1.3 mmHg; p=0.0083, n=6). Restraint stress produced a small but significant increase in BP in inulin/FOS‐fed WKY compared to control (104.5 ± 7.45 vs. 116.3 ± 3.19 mmHg; p=0.0411, n=6). This effect was more pronounced in the SHR on inulin/FOS compared to control diet (189.6 ± 2.1 vs. 198.9 ± 1.9 mmHg; p=0.0024, n=6). These responses were associated with a trend in increase in LF/HF (vasovagal) balance in the diet‐fed WKY (1.99 ± 1.43 vs. 3.04 ± 1.46; p=0.09, n=6), and with significant increase in LF/HF in the diet‐fed SHR (6.49 ± 0.47 vs. 8.16 ± 0.59, p=0.0306, n=6). MEMRI showed increased activation of the PVN (−0.6514 ± 0.07 vs 0.05026 ± 0.06 % of baseline; p=0.0018, n=3) and NTS (0.1194 ± 0.05 vs. 0.3817 ± 0.09 % of baseline; p=0.0409, n=3) in diet‐fed SHR.ConclusionGut microbiota plays an important role in brain‐gut communication in hypertension. This pathway may present a novel therapeutic target for treatment of this condition.Support or Funding InformationFAPESP : Fundação de Amparo à Pesquisa do Estado de São PauloThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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