Department of Anesthesiology, Baylor College of Medicine, Houston, TX, 77030, USA.
Integrative Physiology, Baylor College of Medicine, Houston, TX, 77030, USA.
Sci Rep. 2022 May 20;12(1):8534. doi: 10.1038/s41598-022-12578-7.
Gut dysbiosis, a pathological imbalance of bacteria, has been shown to contribute to the development of hypertension (HT), systemic- and neuro-inflammation, and blood-brain barrier (BBB) disruption in spontaneously hypertensive stroke prone rats (SHRSP). However, to date individual species that contribute to HT in the SHRSP model have not been identified. One potential reason, is that nearly all studies of the SHRSP gut microbiota have analyzed samples from rats with established HT. The goal of this study was to examine the SHRSP gut microbiota before, during, and after the onset of hypertension, and in normotensive WKY control rats over the same age range. We hypothesized that we could identify key microbes involved in the development of HT by comparing WKY and SHRSP microbiota during the pre-hypertensive state and longitudinally. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and fecal microbiota analyzed by16S rRNA gene sequencing. SHRSP showed significant elevations in SBP, as compared to WKY, beginning at 8 weeks of age (p < 0.05 at each time point). Bacterial community structure was significantly different between WKY and SHRSP as early as 4 weeks of age, and remained different throughout the study (p = 0.001-0.01). At the phylum level we observed significantly reduced Firmicutes and Deferribacterota, and elevated Bacteroidota, Verrucomicrobiota, and Proteobacteria, in pre-hypertensive SHRSP, as compared to WKY. At the genus level we identified 18 bacteria whose relative abundance was significantly different in SHRSP versus WKY at the pre-hypertensive ages of 4 or 6 weeks. In an attempt to further refine bacterial candidates that might contribute to the SHRSP phenotype, we compared the functional capacity of WKY versus SHRSP microbial communities. We identified significant differences in amino acid metabolism. Using untargeted metabolomics we found significant reductions in metabolites of the tryptophan-kynurenine pathway and increased indole metabolites in SHRSP versus WKY plasma. Overall, we provide further evidence that gut dysbiosis contributes to hypertension in the SHRSP model, and suggest for the first time the potential involvement of tryptophan metabolizing microbes.
肠道菌群失调，即细菌的病理性失衡，已被证明与自发性高血压卒中易感大鼠（SHRSP）的高血压（HT）、全身性和神经炎症以及血脑屏障（BBB）破坏的发展有关。然而，迄今为止，尚未确定导致 SHRSP 模型中 HT 的单个物种。一个潜在的原因是，几乎所有关于 SHRSP 肠道微生物组的研究都分析了已经患有 HT 的大鼠的样本。本研究的目的是在 SHRSP 出现高血压之前、期间和之后，以及在相同年龄范围内的正常血压 WKY 对照大鼠中，检查 SHRSP 肠道微生物组。我们假设，通过比较高血压前期的 WKY 和 SHRSP 微生物组，我们可以确定与 HT 发展相关的关键微生物。通过尾部血压计测量收缩压（SBP），通过 16S rRNA 基因测序分析粪便微生物组。与 WKY 相比，SHRSP 从 8 周龄开始 SBP 显著升高（每个时间点均 < 0.05）。早在 4 周龄时，WKY 和 SHRSP 之间的细菌群落结构就有显著差异，并且在整个研究过程中一直存在差异（p = 0.001-0.01）。在门水平上，我们观察到在预高血压 SHRSP 中，厚壁菌门和脱硫菌门显著减少，拟杆菌门、疣微菌门和变形菌门显著增加，与 WKY 相比。在属水平上，我们确定了 18 种细菌，它们在 4 或 6 周龄的预高血压年龄时在 SHRSP 与 WKY 之间的相对丰度存在显著差异。为了进一步细化可能导致 SHRSP 表型的细菌候选物，我们比较了 WKY 与 SHRSP 微生物群落的功能能力。我们发现氨基酸代谢存在显著差异。通过非靶向代谢组学，我们发现 SHRSP 与 WKY 血浆中的色氨酸-犬尿氨酸途径代谢物显著减少，吲哚代谢物增加。总体而言，我们提供了进一步的证据表明肠道菌群失调导致 SHRSP 模型中的高血压，并首次提出了色氨酸代谢微生物可能参与的可能性。
Zotero 插件