Neural mechanisms of host-microbiota interaction in hypertension: a potential for bio-electronic medicine

摘要 高血压(HTN)是一种常见的心血管疾病，也是其他心血管疾病的主要危险因素 疾病。如果不进行治疗，HTN可能会导致许多并发症，如中风、痴呆症、糖尿病、 肾脏疾病、阻塞性睡眠呼吸暂停和神经系统疾病。尽管在预防和多种疾病方面取得了进展 在药物治疗方面，相当大比例的患者对目前的治疗仍有抵抗力或顽固性。在大多数 病例中，难治性HTN具有强烈的神经源性，其特征是自主神经功能障碍。 系统(ANS)最近与肠道生物失调有关。然而，HTN中寄主-微生物区系相互作用的机制 没有很好地定义。我们新的初步数据表明，神经-肠道-大脑通讯的崩溃 肠道生物失调可能由迷走神经传入的5-羟色胺能受体信号减少所介导 从肠道到孤束核的投射。在本应用程序中，我们建议使用最先进的 转基因大鼠和人源化大鼠的体内成像、电生理和神经刺激方法 询问健康和HTN中宿主-微生物区系相互作用的特定分子和神经机制，而 评估生物电子医学的隔膜下迷走神经刺激对缓解 HTN患者的肠道生物失调症状。

Abstract Hypertension (HTN) is a prevalent cardiovascular condition and a leading risk factor for other cardiovascular diseases. If it remains untreated, HTN can lead to numerous comorbidities such as stroke, dementia, diabetes, kidney disease, obstructive sleep apnea, and neurological disorders. Despite advances in prevention and multi- drug therapy, a significant proportion of patients remain resistant or refractory to current treatments. In most cases, treatment-resistant HTN is strongly neurogenic, characterized by a dysfunctional autonomic nervous system (ANS) most recently linked to gut dysbiosis. However, mechanisms of host-microbiota interaction in HTN are not well defined. Our new preliminary data suggests that a breakdown in the neural gut-brain communication resulting from gut dysbiosis may be mediated by reduced serotonergic receptor signaling on the vagal afferent projections from the gut to the nucleus of the solitary tract. In this application, we propose to use state of the art in vivo imaging, electrophysiology and neural stimulation approaches in transgenic and humanized rats in order to interrogate specific molecular and neural mechanisms of host-microbiota interaction in health and HTN, while evaluating the potential of sub-diaphragmatic vagal stimulation for bio-electronic medicine to alleviate the symptoms of gut dysbiosis in HTN.