Journal
PHYSIOLOGICAL REPORTS
Volume 3, Issue 12, Pages -Publisher
WILEY
DOI: 10.14814/phy2.12627
Keywords
Gut microbiome; neointimal hyperplasia; short chain fatty acids; sodium butyrate
Categories
Funding
- Department of Surgery at Northwestern University
- Dixon Translational Research Grants Initiative Young Investigator Award
- NIDDK(University of Chicago Digestive Diseases Research Core Center) [P30 DK042086]
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Gut microbial metabolites are increasingly recognized as determinants of health and disease. However, whether host-microbe crosstalk influences peripheral arteries is not understood. Neointimal hyperplasia, a proliferative and inflammatory response to arterial injury, frequently limits the long-term benefits of cardiovascular interventions such as angioplasty, stenting, and bypass surgery. Our goal is to assess the effect of butyrate, one of the principal short chain fatty acids produced by microbial fermentation of dietary fiber, on neointimal hyperplasia development after angioplasty. Treatment of male Lewis Inbred rats with oral vancomycin for 4 weeks changed the composition of gut microbes as assessed by 16S rRNA-based taxonomic profiling and decreased the concentration of circulating butyrate by 69%. In addition, rats treated with oral vancomycin had exacerbated neointimal hyperplasia development after carotid angioplasty. Oral supplementation of butyrate reversed these changes. Butyrate also inhibited vascular smooth muscle cell proliferation, migration, and cell cycle progression in a dose-dependent manner in vitro. Our results suggest for the first time that gut microbial composition is associated with the severity of arterial remodeling after injury, potentially through an inhibitory effect of butyrate on VSMC.
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