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The Role of the Gut Microbiota in Obstructive Sleep Apnea Induced Hypertension
Author(s) -
Durgan David,
Ganesh Bhanu,
Cope Julia,
Ajami Nadim,
Phillips Sharon,
Petrosino Joseph,
Hollister Emily,
Bryan Robert
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.959.2
Subject(s) - obstructive sleep apnea , medicine , gut flora , dysbiosis , blood pressure , feces , population , sleep apnea , endocrinology , physiology , apnea , gastroenterology , immunology , biology , paleontology , environmental health
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 importance of a healthy gut microbiota, and detriment of a dysbiotic microbiota, on host physiology is becoming increasingly evident. We tested the hypothesis that gut dysbiosis contributes to hypertension observed with OSA. Airway obstructions, simulating apneas, were induced by chronically implanting an inflatable obstruction device (OD) in the trachea of rats. Free‐ranging rats underwent 60 apneas/hr (10 sec. each) during 8 hrs of the sleep cycle. Young healthy rats (8 weeks old) on a normal chow diet did not develop hypertension following 2 or 4 weeks of OSA. Additionally, sham rats (underwent surgery without apneas) fed a high fat diet did not develop hypertension. However, when rats were fed a high fat diet for 3 weeks prior to apneas, they exhibited a significant increase in systolic blood pressure after 1 (24mmHg; n=10–13, p<0.05) and 2 weeks (29mmHg; n=10–11, p<0.05) of OSA. Fecal samples were sequenced for the 16S rRNA gene to evaluate the microbiota diversity and composition. Rats fed a high fat diet exhibited a significant increase in the Fimicutes:Bacteroidetes ratio, a well‐established marker of gut dysbiosis, as compared to chow fed rats (n=4–7, p<0.05). Compositional analysis of the gut microbiota revealed that high fat diet significantly decreased several butyrate producing taxa, including a 2.5‐fold reduction of the family Ruminococcaceae (20 vs. 8% of total sequences; n=4–6, p<0.05). Interestingly, oral gavage of the butyrate producing species Clostridium butyricum successfully prevented OSA‐induced hypertension in high fat fed rats. Finally, transplant of dysbiotic cecal contents from hypertensive OSA rats on high fat diet into OSA recipient rats on normal chow diet (shown to be normotensive) resulted in hypertension similar to that which occurred in the donor (see figure, n=4, p<0.05). These studies demonstrate, for the first time, a causal relationship between gut dysbiosis and hypertension, and suggest that manipulation of the microbiota may be a viable treatment for OSA‐induced, and possibly other forms of, hypertension. Support or Funding Information This project was funded by NINDS R01NS080531 (RMB) and by Public Health Service grant DK56338, which funds the Texas Medical Center Digestive Diseases Center (DJD). The hypertensive phenotype of OSA rats is transferable via the gut contentsCecal contents from sham (normotensive) and OSA (hypertensive) rats were gavaged into normotensive recipient rats.