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

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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.