Xiaohong Tracey Gan1, Grace Ettinger1, Cathy X Huang1, Jeremy P Burton1, James V Haist1, Venkatesh Rajapurohitam1, James E Sidaway1, Glynn Martin1, Gregory B Gloor1, Jonathan R Swann1, Gregor Reid1, Morris Karmazyn2. 1. From the Departments of Physiology and Pharmacology (X.T.G., C.X.H., J.V.H., V.R., M.K.), Microbiology and Immunology (G.E., J.P.B., G.R.), Surgery (J.P.B., G.R.), and Biochemistry (G.B.G.), Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Canadian Research and Development Centre for Probiotics, Lawson Health Research Institute, London, Ontario, Canada (G.E., J.P.B., G.B.G., G.R.); and Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, Reading, United Kingdom (J.E.S., G.M., J.R.S.). 2. From the Departments of Physiology and Pharmacology (X.T.G., C.X.H., J.V.H., V.R., M.K.), Microbiology and Immunology (G.E., J.P.B., G.R.), Surgery (J.P.B., G.R.), and Biochemistry (G.B.G.), Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Canadian Research and Development Centre for Probiotics, Lawson Health Research Institute, London, Ontario, Canada (G.E., J.P.B., G.B.G., G.R.); and Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, Reading, United Kingdom (J.E.S., G.M., J.R.S.). Morris.Karmazyn@schulich.uwo.ca.
Abstract
BACKGROUND: Probiotics are extensively used to promote gastrointestinal health, and emerging evidence suggests that their beneficial properties can extend beyond the local environment of the gut. Here, we determined whether oral probiotic administration can alter the progression of postinfarction heart failure. METHODS AND RESULTS: Rats were subjected to 6 weeks of sustained coronary artery occlusion and administered the probiotic Lactobacillus rhamnosus GR-1 or placebo in the drinking water ad libitum. Culture and 16s rRNA sequencing showed no evidence of GR-1 colonization or a significant shift in the composition of the cecal microbiome. However, animals administered GR-1 exhibited a significant attenuation of left ventricular hypertrophy based on tissue weight assessment and gene expression of atrial natriuretic peptide. Moreover, these animals demonstrated improved hemodynamic parameters reflecting both improved systolic and diastolic left ventricular function. Serial echocardiography revealed significantly improved left ventricular parameters throughout the 6-week follow-up period including a marked preservation of left ventricular ejection fraction and fractional shortening. Beneficial effects of GR-1 were still evident in those animals in which GR-1 was withdrawn at 4 weeks, suggesting persistence of the GR-1 effects after cessation of therapy. Investigation of mechanisms showed a significant increase in the leptin:adiponectin plasma concentration ratio in rats subjected to coronary ligation, which was abrogated by GR-1. Metabonomic analysis showed differences between sham control and coronary artery ligated hearts particularly with respect to preservation of myocardial taurine levels. CONCLUSIONS: The study suggests that probiotics offer promise as a potential therapy for the attenuation of heart failure.
BACKGROUND: Probiotics are extensively used to promote gastrointestinal health, and emerging evidence suggests that their beneficial properties can extend beyond the local environment of the gut. Here, we determined whether oral probiotic administration can alter the progression of postinfarction heart failure. METHODS AND RESULTS:Rats were subjected to 6 weeks of sustained coronary artery occlusion and administered the probiotic Lactobacillus rhamnosus GR-1 or placebo in the drinking water ad libitum. Culture and 16s rRNA sequencing showed no evidence of GR-1 colonization or a significant shift in the composition of the cecal microbiome. However, animals administered GR-1 exhibited a significant attenuation of left ventricular hypertrophy based on tissue weight assessment and gene expression of atrial natriuretic peptide. Moreover, these animals demonstrated improved hemodynamic parameters reflecting both improved systolic and diastolic left ventricular function. Serial echocardiography revealed significantly improved left ventricular parameters throughout the 6-week follow-up period including a marked preservation of left ventricular ejection fraction and fractional shortening. Beneficial effects of GR-1 were still evident in those animals in which GR-1 was withdrawn at 4 weeks, suggesting persistence of the GR-1 effects after cessation of therapy. Investigation of mechanisms showed a significant increase in the leptin:adiponectin plasma concentration ratio in rats subjected to coronary ligation, which was abrogated by GR-1. Metabonomic analysis showed differences between sham control and coronary artery ligated hearts particularly with respect to preservation of myocardial taurine levels. CONCLUSIONS: The study suggests that probiotics offer promise as a potential therapy for the attenuation of heart failure.
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