Li Jing, Wang Si-Yuan, Yan Kai-Xin, Wang Pan, Jiao Jie, Wang Yi-Dan, Chen Mu-Lei, Dong Ying, Zhong Jiu-Chang
Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital Capital Medical University Beijing China.
Department of Cardiology, Beijing Chaoyang Hospital Capital Medical University Beijing China.
Imeta. 2024 Jul 18;3(4):e222. doi: 10.1002/imt2.222. eCollection 2024 Aug.
Dysbiosis of the gut microbiota has been implicated in hypertension, and drug-host-microbiome interactions have drawn considerable attention. However, the influence of angiotensin receptor blocker (ARB)-shaped gut microbiota on the host is not fully understood. In this work, we assessed the alterations of blood pressure (BP), vasculatures, and intestines following ARB-modified gut microbiome treatment and evaluated the changes in the intestinal transcriptome and serum metabolome in hypertensive rats. Hypertensive patients with well-controlled BP under ARB therapy were recruited as human donors, spontaneously hypertensive rats (SHRs) receiving normal saline or valsartan were considered animal donors, and SHRs were regarded as recipients. Histological and immunofluorescence staining was used to assess the aorta and small intestine, and 16S rRNA amplicon sequencing was performed to examine gut bacteria. Transcriptome and metabonomic analyses were conducted to determine the intestinal transcriptome and serum metabolome, respectively. Notably, ARB-modified fecal microbiota transplantation (FMT), results in marked decreases in systolic BP levels, collagen deposition and reactive oxygen species accumulation in the vasculature, and alleviated intestinal structure impairments in SHRs. These changes were linked with the reconstruction of the gut microbiota in SHR recipients post-FMT, especially with a decreased abundance of , , and . Moreover, ARB-treated microbes contributed to increased intestinal , , , , and gene levels and decreased and expression were detected in response to ARB-treated microbes. More importantly, circulating metabolites were dramatically reduced in ARB-FMT rats, including 6beta-Hydroxytestosterone and Thromboxane B2. In conclusion, ARB-modified gut microbiota exerts protective roles in vascular remodeling and injury, metabolic abnormality and intestinal dysfunctions, suggesting a pivotal role in mitigating hypertension and providing insights into the cross-talk between antihypertensive medicines and the gut microbiome.
肠道微生物群失调与高血压有关，药物-宿主-微生物组相互作用已引起广泛关注。然而，血管紧张素受体阻滞剂（ARB）塑造的肠道微生物群对宿主的影响尚未完全明确。在本研究中，我们评估了ARB修饰肠道微生物组治疗后血压（BP）、血管和肠道的变化，并评估了高血压大鼠肠道转录组和血清代谢组的变化。招募在ARB治疗下血压控制良好的高血压患者作为人类供体，将接受生理盐水或缬沙坦的自发性高血压大鼠（SHR）视为动物供体，SHR作为受体。采用组织学和免疫荧光染色评估主动脉和小肠，进行16S rRNA扩增子测序检测肠道细菌。分别进行转录组和代谢组分析以确定肠道转录组和血清代谢组。值得注意的是，ARB修饰的粪便微生物群移植（FMT）可导致SHR的收缩压水平显著降低、血管中胶原蛋白沉积和活性氧积累减少，并减轻肠道结构损伤。这些变化与FMT后SHR受体肠道微生物群的重建有关，尤其是与、和丰度降低有关。此外，ARB处理的微生物导致肠道、、、和基因水平升高，并检测到对ARB处理的微生物有反应的和表达降低。更重要的是，ARB-FMT大鼠的循环代谢物显著减少，包括6β-羟基睾酮和血栓素B2。总之，ARB修饰的肠道微生物群在血管重塑和损伤、代谢异常及肠道功能障碍中发挥保护作用，提示其在缓解高血压中起关键作用，并为抗高血压药物与肠道微生物组之间的相互作用提供了见解。
