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

高血压宿主-微生物群相互作用的神经机制：生物电子医学的潜力

• 批准号: 10331828
• 负责人: Jasenka Zubcevic
• 金额: $ 43.99万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10331828
• 关键词: Address; Affect; Afferent Neurons; American; Anatomy; Animals; Autonomic nervous system; Blood Pressure; Brain; Calcium; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Chronic; Colon; Data; Dementia; Diabetes Mellitus; Disease; Effectiveness; Electric Stimulation; Electrophysiology (science); Event; Feedback; Fiber; Functional disorder; Future; HTR3A gene; Health; Human; Hypertension; Impairment; Investigation; Kidney Diseases; Lead; Length; Life Style Modification; Link; Maps; Mediating; Medicine; Modeling; Molecular; Monitor; Nerve; Neurons; Nodose Ganglion; Norepinephrine; Nucleus solitarius; Obstructive Sleep Apnea; Outcome; Patients; Pattern; Pharmacotherapy; Plasma; Prevention; Production; Public Health; Rattus; Receptor Signaling; Reflex action; Refractory; Regulation; Research; Resistance; Resistant Hypertension; Respiratory Diaphragm; Risk Factors; Rodent; Role; Serotonin; Signal Transduction; Site; Stroke; Telemetry; Therapeutic; Time; Tracer; Transgenic Organisms; Transplantation; Vasomotor; Viral; aggressive therapy; blood pressure elevation; blood pressure reduction; comorbidity; dysbiosis; experimental study; fecal transplantation; gut dysbiosis; gut microbiota; gut-brain axis; host microbiota; human microbiota; hypertension treatment; hypertensive; improved; in vivo imaging; innovation; microbiota; nerve supply; nervous system disorder; neural stimulation; neuromechanism; normotensive; novel; optogenetics; prevent; receptor; reduce symptoms; relating to nervous system; response; social; translational impact; translational model

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.

抽象的 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。如果不及时治疗，高血压会导致多种合并症，如中风、痴呆、糖尿病、 肾脏疾病、阻塞性睡眠呼吸暂停和神经系统疾病。尽管在预防和多方面取得了进展 药物治疗后，很大一部分患者对当前治疗仍具有耐药性或难治性。在大多数 在病例中，治疗抵抗性高血压具有强烈的神经源性，其特征是自主神经功能失调 系统（ANS）最近与肠道菌群失调有关。然而，HTN 中宿主-微生物群相互作用的机制 没有明确定义。我们的新初步数据表明，神经肠脑通讯出现故障 肠道菌群失调导致的肠道菌群失调可能是由迷走神经传入神经上的血清素受体信号传导减少介导的 从肠道到孤束核的投射。在此应用中，我们建议使用最先进的 转基因和人源化大鼠的体内成像、电生理学和神经刺激方法 探究健康和高血压中宿主-微生物群相互作用的特定分子和神经机制，同时 评估膈下迷走神经刺激在生物电子医学中缓解 HTN 肠道菌群失调的症状。