Welathanthree Malindi, Keating Damien J, Macefield Vaughan G, Carnevale Daniela, Marques Francine Z, R Muralitharan Rikeish
Hypertension Research Laboratory, Victorian Heart Institute and Department of Pharmacology, Monash Biomedicine Discovery Institute, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Melbourne, Australia.
Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia.
Clin Sci (Lond). 2025 May 8;139(9):431-47. doi: 10.1042/CS20240787.
Hypertension, or high blood pressure (BP), is a widespread condition affecting one in three adults globally. Despite the availability of treatment options, 50% of hypertensive patients in countries such as Australia fail to achieve adequate BP control, often due to a lack of response to current therapies. Diet plays a crucial role in BP regulation. A high-fibre diet reduces BP through the gut microbiome and the production of microbial metabolites known as short-chain fatty acids (SCFAs). However, the mechanisms of BP regulation by SCFAs remained still unclear. A novel hypothesis we explore in this review is that these microbial metabolites may regulate BP via the activation of central mechanisms, a phenomenon called the gut-brain axis. While substantial evidence in animal models and humans supports the protective role of SCFAs in hypertension, the precise mechanisms remain unclear. SCFA stimulates the release of neurotransmitters and hormones such as serotonin, cholecystokinin, glucagon-like peptide 1 and peptide YY by enteroendocrine cells, a rare population of cells lining the gastrointestinal tract. These hormones bind to their receptors on the peripheral nervous system nerves, such as the vagus and spinal nerves, conveying information to the brain. The mechanisms by which information is relayed from the gut microbiome to the brain likely involve the immune system and gut-derived neurotransmitters and hormones. A deeper understanding of these pathways and mechanisms will facilitate the development of novel therapeutics for hypertension and other cardiovascular diseases.
高血压，即血压升高，是一种普遍存在的疾病，全球每三个成年人中就有一人受其影响。尽管有多种治疗选择，但在澳大利亚等国家，50%的高血压患者未能实现血压的充分控制，这通常是由于对当前治疗方法缺乏反应所致。饮食在血压调节中起着至关重要的作用。高纤维饮食通过肠道微生物群以及称为短链脂肪酸（SCFAs）的微生物代谢产物的产生来降低血压。然而，SCFAs调节血压的机制仍不清楚。在本综述中，我们探讨的一个新假说是，这些微生物代谢产物可能通过激活中枢机制来调节血压，这种现象称为肠脑轴。虽然动物模型和人类的大量证据支持SCFAs在高血压中的保护作用，但其确切机制仍不清楚。SCFAs刺激胃肠道内分泌细胞释放神经递质和激素，如血清素、胆囊收缩素、胰高血糖素样肽1和肽YY，这些细胞是胃肠道内衬的稀有细胞群体。这些激素与外周神经系统神经（如迷走神经和脊神经）上的受体结合，将信息传递到大脑。从肠道微生物群向大脑传递信息的机制可能涉及免疫系统以及肠道衍生的神经递质和激素。对这些途径和机制的更深入理解将有助于开发针对高血压和其他心血管疾病的新型疗法。
