Vancomycin treatment and butyrate supplementation modulate gut microbe composition and severity of neointimal hyperplasia after arterial injury

Abstract

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.

The Future of Vascular Biology and Medicine

“…Butyrate limited neointimal formation through a mechanism that involved decreased aortic smooth muscle cell proliferation, cell cycle progression, and migration. 45 …”

Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty acids

“…9 Disruption of the microbiome after antibiotic treatment results in an altered metabolome with attenuated production of SCFAs. 10,11 We hypothesized that a reduction of SCFA metabolites in vancomycin-treated mice contributes to their enhanced susceptibility to allergic airway inflammation.…”

Resveratrol and the Interaction between Gut Microbiota and Arterial Remodelling

“…Butyrate also inhibits superoxide production and consequent Nod-like receptor pyrin domain 3 (Nlrp3) inflammasome formation and activation, which is beneficial against vascular inflammation or intimal hyperplasia [126]. These studies suggest that the association of gut microbial composition with arterial remodelling could potentially occur through an inhibitory effect of butyrate on VSMCs [125].…”

“…Olfr78 is found in olfactory neurons, renal afferent arterioles and in VSMC, where it plays a role in blood pressure regulation [124]. In rats, oral vancomycin treatment exacerbates neointimal hyperplasia development after carotid angioplasty [125]. However, oral supplementation of butyrate can reverse these changes and inhibit VSMC proliferation, migration, and cell cycle progression in a dose-dependent manner in vitro.…”