A human‐origin probiotics cocktail exhibit cardio‐protective effects independent of GLP‐1 receptor signaling

Abstract

The emerging role of the gut microbiome in cardiovascular diseases is posited to be mediated by the microbial metabolites, some of which yield beneficial effects while others may accelerate the heart diseases. The beneficial metabolites like short‐chain fatty acids, particularly butyrate, exhibit several beneficial effects on metabolic diseases including cardiovascular functions. We have previously demonstrated that butyrate promotes the production of glucagon‐like protein‐1 (GLP‐1). GLP‐1 and its therapeutic agonists are known to promote cardiovascular functions. Herein, we investigated the role of systemic deletion of GLP‐1 receptor (using GLP1R KO) on cardiac functions in 16 weeks high‐fat diet (HFD)‐fed obese mice and assessed the impact of feeding a butyrate‐producing probiotic cocktail (consisting 5 Lactobacillus and 5 Enterococcus strains isolated from infant's gut) on cardiac functions, using the non‐invasive high‐frequency ultrasound echocardiography system (VEVO, VisualSonics, Toronto, Ontario, Canada). GLP1R‐KO mice show reduced cardiac output and stroke volume, and higher ejection fraction and fractional shortening of the left ventricle compared GLP1R‐WT mice. In addition, the GLP1R‐KO mice also exhibited significantly reduced systolic and diastolic diameter and volume, along with higher ratio of aortic acceleration and ejection time. Interestingly, feeding of probiotic cocktail protected from such dysfunctions in GLP‐KO mice, and also all these measures remain unchanged in GLP‐WT mice with and without probiotics treatments. No significant differences in body weight and diet intake was observed, however, glucose and insulin tolerance tests were improved in both probiotic‐fed groups. Results indicate that GLP1‐receptor depletion causes cardiovascular dysfunctions and feeding of the human‐origin probiotic cocktail ameliorates such dysfunctions, and probiotics effects are independent of GLP‐1 receptor signaling. Further analyses to better understand the mechanisms of actions of probiotics cocktail contributing these effects, are directed to establish a new cardioprotective probiotic biotherapy in obesity and type 2 diabetes.Support or Funding InformationWe thank the support provide by Center of Cardiovascular Sciences Center, Wake Forest School of Medicine, and the Department of Defense funding PR170446, as well funds and services provided from Center for Diabetes, Obesity and Metabolism, Wake Forest Baptist Medical Center and National Center for Advancing Translational Sciences (NCATS), National Institutes of Health funded Wake Forest Clinical and Translational Science Institute (WF CTSI) through Grant Award Number UL1TR001420.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.