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肠道微生物群、高血压和肾脏疾病之间的相互作用:短链脂肪酸的作用。

The interplay among gut microbiota, hypertension and kidney diseases: The role of short-chain fatty acids.

机构信息

Department of Immunology, Institute of Biomedical Science, Universidade de São Paulo, São Paulo, Brazil; Department of Medicine, Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil.

Department of Physiology and Biophysics, Institute of Biomedical Science, Universidade de São Paulo, São Paulo, Brazil.

出版信息

Pharmacol Res. 2019 Mar;141:366-377. doi: 10.1016/j.phrs.2019.01.019. Epub 2019 Jan 10.

Abstract

The bacteria community living in the gut maintains a symbiotic relationship with the host and its unbalance has been associated with progression of a wide range of intestinal and extra intestinal conditions. Hypertension and chronic kidney disease (CKD) are closely associated diseases with high incidence rates all over the world. Increasing data have supported the involvement of gut microbiome in the blood pressure regulation and the impairment of CKD prognosis. In hypertension, the reduced number of short-chain fatty acids (SCFAs) producing bacteria is associated with modifications in gut environment, involving reduction of the hypoxic gut profile and worsening of the microbial balance, leading to a loss of epithelial barrier integrity, development of gut inflammation and the reduction of SCFAs plasma levels. These modifications compromise the blood pressure regulation and, as a consequence, favor the end organ damage, also affecting the kidneys. In CKD, impaired renal function leads to accumulation of high levels of uremic toxins that reach the intestine and cause alterations in bacteria composition and fecal metabolite profile, inducing a positive feedback that allows translocation of endotoxins into the bloodstream, which enhances local kidney inflammation and exacerbate kidney injury, compromising even more CKD prognosis. In line with these data, the use of prebiotics, probiotics and fecal microbiota transplantation are becoming efficient therapies to improve the gut dysbiosis aiming hypertension and CKD treatment. This review describes how changes in gut microbiota composition can affect the development of hypertension and the progression of kidney diseases, highlighting the importance of the gut microbial composition uncovering to improve human health maintenance and, especially, for the development of new alternative therapies.

摘要

肠道中存在的细菌群落与宿主保持着共生关系,其失衡与多种肠道和肠道外疾病的进展有关。高血压和慢性肾脏病(CKD)是密切相关的疾病,在全球范围内发病率都很高。越来越多的数据支持肠道微生物组参与血压调节和 CKD 预后的损害。在高血压中,产生短链脂肪酸(SCFA)的细菌数量减少与肠道环境的改变有关,涉及缺氧肠道特征的减少和微生物平衡的恶化,导致上皮屏障完整性的丧失、肠道炎症的发展和 SCFA 血浆水平的降低。这些改变会影响血压调节,从而导致终末器官损伤,也会影响肾脏。在 CKD 中,肾功能受损会导致高水平的尿毒症毒素积累,这些毒素到达肠道并导致细菌组成和粪便代谢物特征的改变,引发正反馈,使内毒素易位到血液中,从而增强局部肾脏炎症,加重肾脏损伤,进一步影响 CKD 的预后。根据这些数据,使用益生元、益生菌和粪便微生物移植正在成为改善高血压和 CKD 治疗中肠道失调的有效治疗方法。本文综述了肠道微生物组成的变化如何影响高血压的发展和肾脏疾病的进展,强调了肠道微生物组成的重要性,以改善人类健康维护,特别是开发新的替代治疗方法。

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