Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.
Department of Psychiatry, College of Medicine, University of Florida, Gainesville, Florida.
Acta Physiol (Oxf). 2019 Jun;226(2):e13256. doi: 10.1111/apha.13256. Epub 2019 Feb 20.
Butyrate is a major gut microbiota-derived metabolite. Reduced butyrate-producing bacteria has been reported in the spontaneously hypertensive rat (SHR), a model of hypertension characterized by dysfunctional autonomic nervous system and gut dysbiosis. Here, we demonstrate a potential mechanism for butyrate in blood pressure regulation.
High-performance liquid chromatography and liquid chromatography-mass spectrometry were performed to measure butyrate levels in feces and serum. Ussing chamber determined butyrate transport in colon ex vivo. Real-time PCR and immunohistochemistry evaluated expression of butyrate transporter, Slc5a8, in the colon. Mean arterial blood pressure was measured in catheterized anesthetized rats before and after a single butyrate intracerebroventricular injection. Activity of cardioregulatory brain regions was determined by functional magnetic resonance imaging to derive neural effects of butyrate.
In the SHR, we demonstrated elevated butyrate levels in cecal content, but diminished butyrate levels in circulation, possibly due to reduced expression of Slc5a8 transporter in the colon. In addition, we observed lower expression levels of butyrate-sensing receptors in the hypothalamus of SHR, likely leading to the reduced effects of centrally administered butyrate on blood pressure in the SHR. Functional magnetic resonance imaging revealed reduced activation of cardioregulatory brain regions following central administration of butyrate in the SHR compared to control.
We demonstrated a reduced availability of serum butyrate in the SHR, possibly due to diminished colonic absorption. Reduced expression of butyrate-sensing receptors in the SHR hypothalamus may explain the reduced central responsiveness to butyrate, indicating microbial butyrate may play a role in blood pressure regulation.
丁酸是主要的肠道微生物衍生代谢物。在自发性高血压大鼠（SHR）中，已报道丁酸产生菌减少，SHR 是一种自主神经系统功能障碍和肠道菌群失调的高血压模型。在这里，我们展示了丁酸在血压调节中的潜在机制。
采用高效液相色谱和液相色谱-质谱法测定粪便和血清中的丁酸水平。Ussing 室测定结肠的体外丁酸转运。实时 PCR 和免疫组织化学评估结肠中丁酸转运体 Slc5a8 的表达。在麻醉大鼠导管插入前后，经侧脑室单次给予丁酸，测量平均动脉血压。通过功能磁共振成像测定心脏调节脑区的活性，以得出丁酸的神经效应。
在 SHR 中，我们发现在盲肠内容物中丁酸水平升高，但在循环中丁酸水平降低，可能是由于结肠中 Slc5a8 转运体的表达减少所致。此外，我们观察到 SHR 下丘脑中丁酸感应受体的表达水平较低，这可能导致中枢给予丁酸对 SHR 血压的影响降低。功能磁共振成像显示，与对照组相比，中枢给予丁酸后 SHR 心脏调节脑区的激活减少。
我们证明了 SHR 血清中丁酸的可用性降低，可能是由于结肠吸收减少所致。SHR 下丘脑中丁酸感应受体的表达减少可能解释了对丁酸的中枢反应性降低，表明微生物丁酸可能在血压调节中发挥作用。
