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Inulin-FOS rich diet alters gut microbiota, brain activity and cardiovascular response in spontaneously hypertensive rats (SHR)

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Carla Grazielle Bueno Silva
Total Authors: 1
Document type: Doctoral Thesis
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
Defense date:
Examining board members:
Mario José Abdalla Saad; Maria Carolina Santos Mendes; Andrey dos Santos; Carla Roberta de Oliveira Carvalho; Bruno de Melo Carvalho
Advisor: Mario José Abdalla Saad

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 blood pressure (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. Methods: Male 4 weeks old WKY and SHR were fed with 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. Results: Inulin/FOS-rich diet caused significant shifts in gut bacterial profiles in WKY and SHR (e.g. Bifidobacterium population increased in diet-fed WKY: 0.006624 ± 0.0018 vs. 0.4989 ± 0.1745, n=6; p=0.0073, n=6, and diet-fed SHR: 0.03099 ± 0.0127 vs. 0.2134 ± 0.0656; 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 BP compared to control (163.8 ± 1.6 vs. 169.6 ± 1.3; 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 mmHg 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; 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 a 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; p=0.0018, n=3) and NTS (0.1194 ± 0.05 ± 0.3817 ± 0.09; p=0.0409, n=3) in diet-fed SHR. Conclusion: Gut microbiota plays an important role in brain-gut communication in hypertension. This presents a novel therapeutic target for treatment of hypertension (AU)

FAPESP's process: 16/04723-5 - The influence of gut microbiota in blood pressure modulation of rodents: the role of hydrogen sulfide (H2S) and short-chain fatty acids.
Grantee:Carla Grazielle Bueno Silva
Support Opportunities: Scholarships in Brazil - Doctorate