The role of the gut microbiome in obstructive sleep apnea induced hypertension
Description: Obstructive sleep apnea (OSA), characterized by repeated closure of the upper airway during sleep, is a significant clinical problem affecting upwards of 25% of the adult population in the United States. OSA has been shown to be an independent risk factor for systemic hypertension, and the most common underlying cause of resistant hypertension. The pathologic cascade linking OSA to hypertension is not fully understood. I will test the central hypothesis that OSA-induced hypertension results from gut dysbiosis. Gut dysbiosis, a pathological alteration in the ecological community of the gut, is becoming recognized as an underlying cause of pathological states in organ systems beyond the GI system. Using a rat model of OSA, I have demonstrated that (1) rats on a high fat diet develop hypertension within one week of initiating OSA; (2) OSA-induced hypertension is associated with gut dysbiosis; (3) hypertension is induced in normotensive rats after receiving microbiota from hypertensive OSA rats; (4) OSA-induced hypertension can be prevented by manipulating the gut microbiota. Based on this strong preliminary evidence, I now propose the following specific aims. Aim 1. Define the changes to the gut microbiota following OSA, and determine if clinically relevant methods of manipulating the microbiota (probiotics) can prevent the development of OSA-induced hypertension. Aim 2. Determine if OSA results in increased gut permeability and inflammation that can be linked to the development of hypertension. Aim 3. Determine if the adverse effects of OSA on the gut and blood pressure are reversible. This novel hypothesis points to the GI tract and gut microbiota as the underlying cause of OSA-induced hypertension. My preliminary data demonstrating that the hypertensive phenotype can be transferred to a normotensive rat, via gut contents transplant, is the first to directly link the gut to blood pressure regulation. Establishing a role for the GI tract as a potential cause for hypertension represents a paradigm shift in our thinking. If valid, then new and novel therapeutic interventions could be used to alter the gut microbiota for the prevention of OSA-induced hypertension.
Funder: American Heart Association
Amount: $231,000
Funding type: fellowship
Funder scheme: Scientist Development Grant
Start date: 2016-07-01
End date: 2019-06-30
Investigators: David Durgan, David Durgan
Institution: Baylor College of Medicine
Funded outputs count: 6
Funder award ID: 16SDG29970000
OpenAlex ID: G2460150010