GutHeart: Targeting Gut Microbiota to Treat Heart Failure

Summary

The objective of this trial is to study the effect of targeting the gut microbiota in patients with heart failure (HF). First, the investigators will characterize gut microbiota composition in patients with various degree of systolic HF as compared with healthy controls. Second, the potential impact of targeting gut microbiota to improve HF will be investigated through an open label randomized controlled trial (RCT) of probiotics, antibiotics and controls. The hypothesis being tested is that the gut microbiota is altered in HF; that gut microbiota of HF patients, through interaction with the intestinal and systemic innate immune system, contribute to a low-grade systemic inflammation as well as metabolic disturbances in these patients; and that an intervention with probiotics and the non-absorbable antibiotic Rifaximin attenuates these inflammatory and metabolic disturbances and improves heart function through modulation of the gut microbiota.

Timeline

Start

2016-03-11

Primary completion

2019-06-20

Completion

2019-12-31

Publications

• Background Aukrust P, Yndestad A, Ueland T, Damas JK, Gullestad L. Anti-inflammatory trials in chronic heart failure. Heart Fail Monit. 2006;5(1):2-9.
• Background Backhed F. Meat-metabolizing bacteria in atherosclerosis. Nat Med. 2013 May;19(5):533-4. doi: 10.1038/nm.3178. No abstract available.
• Background Vinje S, Stroes E, Nieuwdorp M, Hazen SL. The gut microbiome as novel cardio-metabolic target: the time has come! Eur Heart J. 2014 Apr;35(14):883-7. doi: 10.1093/eurheartj/eht467. Epub 2013 Nov 11.
• Background Charalambous BM, Stephens RC, Feavers IM, Montgomery HE. Role of bacterial endotoxin in chronic heart failure: the gut of the matter. Shock. 2007 Jul;28(1):15-23. doi: 10.1097/shk.0b013e318033ebc5.
• Background Genth-Zotz S, von Haehling S, Bolger AP, Kalra PR, Wensel R, Coats AJ, Anker SD. Pathophysiologic quantities of endotoxin-induced tumor necrosis factor-alpha release in whole blood from patients with chronic heart failure. Am J Cardiol. 2002 Dec 1;90(11):1226-30. doi: 10.1016/s0002-9149(02)02839-4.
• Background Sandek A, Anker SD, von Haehling S. The gut and intestinal bacteria in chronic heart failure. Curr Drug Metab. 2009 Jan;10(1):22-8. doi: 10.2174/138920009787048374.
• Background Troseid M, Ueland T, Hov JR, Svardal A, Gregersen I, Dahl CP, Aakhus S, Gude E, Bjorndal B, Halvorsen B, Karlsen TH, Aukrust P, Gullestad L, Berge RK, Yndestad A. Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J Intern Med. 2015 Jun;277(6):717-26. doi: 10.1111/joim.12328. Epub 2014 Dec 1.
• Background Conraads VM, Jorens PG, De Clerck LS, Van Saene HK, Ieven MM, Bosmans JM, Schuerwegh A, Bridts CH, Wuyts F, Stevens WJ, Anker SD, Rauchhaus M, Vrints CJ. Selective intestinal decontamination in advanced chronic heart failure: a pilot trial. Eur J Heart Fail. 2004 Jun;6(4):483-91. doi: 10.1016/j.ejheart.2003.12.004.
• Background Fox MA, Peterson S, Fabri BM, van Saene HK. Selective decontamination of the digestive tract in cardiac surgical patients. Crit Care Med. 1991 Dec;19(12):1486-90. doi: 10.1097/00003246-199112000-00008.
• Background Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.1056/NEJMoa1109400.
• Background Gan XT, Ettinger G, Huang CX, Burton JP, Haist JV, Rajapurohitam V, Sidaway JE, Martin G, Gloor GB, Swann JR, Reid G, Karmazyn M. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat. Circ Heart Fail. 2014 May;7(3):491-9. doi: 10.1161/CIRCHEARTFAILURE.113.000978. Epub 2014 Mar 13.
• Background McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010 May 14;16(18):2202-22. doi: 10.3748/wjg.v16.i18.2202.
• Background Costanza AC, Moscavitch SD, Faria Neto HC, Mesquita ET. Probiotic therapy with Saccharomyces boulardii for heart failure patients: a randomized, double-blind, placebo-controlled pilot trial. Int J Cardiol. 2015 Jan 20;179:348-50. doi: 10.1016/j.ijcard.2014.11.034. Epub 2014 Nov 11. No abstract available.
• Background ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available.
• Background Sugrue DD, Rodeheffer RJ, Codd MB, Ballard DJ, Fuster V, Gersh BJ. The clinical course of idiopathic dilated cardiomyopathy. A population-based study. Ann Intern Med. 1992 Jul 15;117(2):117-23. doi: 10.7326/0003-4819-117-2-117.
• Raju SC, Molinaro A, Awoyemi A, Jorgensen SF, Braadland PR, Nendl A, Seljeflot I, Ueland PM, McCann A, Aukrust P, Vestad B, Mayerhofer C, Broch K, Gullestad L, Lappegard KT, Halvorsen B, Kristiansen K, Hov JR, Troseid M. Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity. Genome Med. 2024 Feb 8;16(1):27. doi: 10.1186/s13073-024-01296-6.

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Indications