Intestinal barrier dysfunction as a therapeutic target for cardiovascular disease

Am J Physiol Heart Circ Physiol. 2020 Dec 1;319(6):H1227-H1233. doi: 10.1152/ajpheart.00612.2020. Epub 2020 Sep 28.


The gut microbiome and intestinal dysfunction have emerged as potential contributors to the development of cardiovascular disease (CVD). Alterations in gut microbiome are well documented in hypertension, atherosclerosis, and heart failure and have been investigated as a therapeutic target. However, a perhaps underappreciated but related role for intestinal barrier function has become evident. Increased intestinal permeability is observed in patients and mouse models of CVD. This increased intestinal permeability can enhance systemic inflammation, alter gut immune function, and has been demonstrated as predictive of adverse cardiovascular outcomes. The goal of this review is to examine the evidence supporting a role for intestinal barrier function in cardiovascular disease and its prospect as a novel therapeutic target. We outline key studies that have investigated intestinal permeability in hypertension, coronary artery disease, atherosclerosis, heart failure, and myocardial infarction. We highlight the central mechanisms involved in the breakdown of barrier function and look at emerging evidence for restored barrier function as a contributor to promising treatment strategies such as short chain fatty acid, probiotic, and renin angiotensin system-targeted therapeutics. Recent studies of more selective targeting of the intestinal barrier to improve disease outcomes are also examined. We suggest that although current data supporting a contribution of intestinal permeability to CVD pathogenesis are largely associative, it appears to be a promising avenue for further investigation. Additional studies of the mechanisms of barrier restoration in CVD and testing of intestinal barrier-targeted compounds will be required to confirm their potential as a new class of CVD therapeutic.

Keywords: atherosclerosis; cardiovascular disease; gut microbiome; hypertension; intestinal permeability.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cardiovascular Agents / therapeutic use*
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / microbiology
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular System / drug effects*
  • Cardiovascular System / physiopathology
  • Gastrointestinal Agents / therapeutic use*
  • Gastrointestinal Microbiome / drug effects*
  • Humans
  • Intestinal Absorption / drug effects*
  • Intestines / drug effects*
  • Intestines / microbiology
  • Intestines / physiopathology
  • Permeability


  • Cardiovascular Agents
  • Gastrointestinal Agents