Intestinal Microbiota Transplantation in Patients With Chronic Heart Failure

Summary

The purpose of this study is to determine whether people with CHF, who often have different gut bacteria from healthy, would benefit from replacing their gut bacteria with healthy donor bacteria (also known as Intestinal Microbiota Transplantation - IMT). IMT aims to restore healthy gut bacteria in patients with CHF, with previous studies showing its effectiveness, but further research is needed. IMT is an approved treatment for patients with infectious diarrhea. More than 10,000 IMTs are performed every year in the US. However IMT is not approved for patients with CHF, and thus considered investigational.

Timeline

Start

2025-09-01

Primary completion

2027-09

Completion

2027-11

Publications

• Background Savarese G, Lund LH. Global Public Health Burden of Heart Failure. Card Fail Rev. 2017 Apr;3(1):7-11. doi: 10.15420/cfr.2016:25:2.
• Background Roger VL. Epidemiology of heart failure. Circ Res. 2013 Aug 30;113(6):646-59. doi: 10.1161/CIRCRESAHA.113.300268.
• Background Francis GS, Benedict C, Johnstone DE, Kirlin PC, Nicklas J, Liang CS, Kubo SH, Rudin-Toretsky E, Yusuf S. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation. 1990 Nov;82(5):1724-9. doi: 10.1161/01.cir.82.5.1724.
• Background Munger MA, Johnson B, Amber IJ, Callahan KS, Gilbert EM. Circulating concentrations of proinflammatory cytokines in mild or moderate heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1996 Apr 1;77(9):723-7. doi: 10.1016/s0002-9149(97)89206-5.
• Background Testa M, Yeh M, Lee P, Fanelli R, Loperfido F, Berman JW, LeJemtel TH. Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension. J Am Coll Cardiol. 1996 Oct;28(4):964-71. doi: 10.1016/s0735-1097(96)00268-9.
• Background Kummen M, Mayerhofer CCK, Vestad B, Broch K, Awoyemi A, Storm-Larsen C, Ueland T, Yndestad A, Hov JR, Troseid M. Gut Microbiota Signature in Heart Failure Defined From Profiling of 2 Independent Cohorts. J Am Coll Cardiol. 2018 Mar 13;71(10):1184-1186. doi: 10.1016/j.jacc.2017.12.057. No abstract available.
• Background Khoruts A, Brandt LJ. Fecal Microbiota Transplant: A Rose by Any Other Name. Am J Gastroenterol. 2019 Jul;114(7):1176. doi: 10.14309/ajg.0000000000000286. No abstract available.
• Background Colombo PC, Ganda A, Lin J, Onat D, Harxhi A, Iyasere JE, Uriel N, Cotter G. Inflammatory activation: cardiac, renal, and cardio-renal interactions in patients with the cardiorenal syndrome. Heart Fail Rev. 2012 Mar;17(2):177-90. doi: 10.1007/s10741-011-9261-3.
• Background Kjekshus J, Apetrei E, Barrios V, Bohm M, Cleland JG, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Janosi A, Kamensky G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J; CORONA Group. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007 Nov 29;357(22):2248-61. doi: 10.1056/NEJMoa0706201. Epub 2007 Nov 5.
• Background Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G; Gissi-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Oct 4;372(9645):1231-9. doi: 10.1016/S0140-6736(08)61240-4. Epub 2008 Aug 29.
• Background Mann DL, McMurray JJ, Packer M, Swedberg K, Borer JS, Colucci WS, Djian J, Drexler H, Feldman A, Kober L, Krum H, Liu P, Nieminen M, Tavazzi L, van Veldhuisen DJ, Waldenstrom A, Warren M, Westheim A, Zannad F, Fleming T. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation. 2004 Apr 6;109(13):1594-602. doi: 10.1161/01.CIR.0000124490.27666.B2. Epub 2004 Mar 15.
• Background Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT; Anti-TNF Therapy Against Congestive Heart Failure Investigators. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003 Jul 1;107(25):3133-40. doi: 10.1161/01.CIR.0000077913.60364.D2. Epub 2003 Jun 9.
• Background Ellekilde M, Selfjord E, Larsen CS, Jakesevic M, Rune I, Tranberg B, Vogensen FK, Nielsen DS, Bahl MI, Licht TR, Hansen AK, Hansen CH. Transfer of gut microbiota from lean and obese mice to antibiotic-treated mice. Sci Rep. 2014 Aug 1;4:5922. doi: 10.1038/srep05922.
• Background Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23. doi: 10.1073/pnas.0407076101. Epub 2004 Oct 25.
• Background Backhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):979-84. doi: 10.1073/pnas.0605374104. Epub 2007 Jan 8.
• Background Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 Dec 21;444(7122):1022-3. doi: 10.1038/4441022a.
• Background Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI. A core gut microbiome in obese and lean twins. Nature. 2009 Jan 22;457(7228):480-4. doi: 10.1038/nature07540. Epub 2008 Nov 30.
• Background Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec 21;444(7122):1027-31. doi: 10.1038/nature05414.
• Background Tang WH, Kitai T, Hazen SL. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017 Mar 31;120(7):1183-1196. doi: 10.1161/CIRCRESAHA.117.309715.
• Background Luedde M, Winkler T, Heinsen FA, Ruhlemann MC, Spehlmann ME, Bajrovic A, Lieb W, Franke A, Ott SJ, Frey N. Heart failure is associated with depletion of core intestinal microbiota. ESC Heart Fail. 2017 Aug;4(3):282-290. doi: 10.1002/ehf2.12155. Epub 2017 Apr 21.
• Background Sandek A, Bauditz J, Swidsinski A, Buhner S, Weber-Eibel J, von Haehling S, Schroedl W, Karhausen T, Doehner W, Rauchhaus M, Poole-Wilson P, Volk HD, Lochs H, Anker SD. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007 Oct 16;50(16):1561-9. doi: 10.1016/j.jacc.2007.07.016. Epub 2007 Oct 1.
• Background Pasini E, Aquilani R, Testa C, Baiardi P, Angioletti S, Boschi F, Verri M, Dioguardi F. Pathogenic Gut Flora in Patients With Chronic Heart Failure. JACC Heart Fail. 2016 Mar;4(3):220-7. doi: 10.1016/j.jchf.2015.10.009. Epub 2015 Dec 9.
• Background Cui X, Ye L, Li J, Jin L, Wang W, Li S, Bao M, Wu S, Li L, Geng B, Zhou X, Zhang J, Cai J. Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients. Sci Rep. 2018 Jan 12;8(1):635. doi: 10.1038/s41598-017-18756-2.
• Background Kamo T, Akazawa H, Suda W, Saga-Kamo A, Shimizu Y, Yagi H, Liu Q, Nomura S, Naito AT, Takeda N, Harada M, Toko H, Kumagai H, Ikeda Y, Takimoto E, Suzuki JI, Honda K, Morita H, Hattori M, Komuro I. Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure. PLoS One. 2017 Mar 22;12(3):e0174099. doi: 10.1371/journal.pone.0174099. eCollection 2017.
• Background Sandek A, Swidsinski A, Schroedl W, Watson A, Valentova M, Herrmann R, Scherbakov N, Cramer L, Rauchhaus M, Grosse-Herrenthey A, Krueger M, von Haehling S, Doehner W, Anker SD, Bauditz J. Intestinal blood flow in patients with chronic heart failure: a link with bacterial growth, gastrointestinal symptoms, and cachexia. J Am Coll Cardiol. 2014 Sep 16;64(11):1092-102. doi: 10.1016/j.jacc.2014.06.1179.
• Background Jennings DL, Bohn B, Zuver A, Onat D, Gaine M, Royzman E, Hupf J, Brunjes D, Latif F, Restaino S, Garan AR, Topkara VK, Takayama H, Takeda K, Naka Y, Farr M, Nandakumar R, Uhlemann AC, Colombo PC, Demmer RT, Yuzefpolskaya M. Gut microbial diversity, inflammation, and oxidative stress are associated with tacrolimus dosing requirements early after heart transplantation. PLoS One. 2020 May 29;15(5):e0233646. doi: 10.1371/journal.pone.0233646. eCollection 2020.
• Background Yuzefpolskaya M, Bohn B, Nasiri M, Zuver AM, Onat DD, Royzman EA, Nwokocha J, Mabasa M, Pinsino A, Brunjes D, Gaudig A, Clemons A, Trinh P, Stump S, Giddins MJ, Topkara VK, Garan AR, Takeda K, Takayama H, Naka Y, Farr MA, Nandakumar R, Uhlemann AC, Colombo PC, Demmer RT. Gut microbiota, endotoxemia, inflammation, and oxidative stress in patients with heart failure, left ventricular assist device, and transplant. J Heart Lung Transplant. 2020 Sep;39(9):880-890. doi: 10.1016/j.healun.2020.02.004. Epub 2020 Feb 13.
• Background Yuzefpolskaya M, Lumish HS, Javaid A, Cagliostro B, Mondellini GM, Bohn B, Sweat A, Onat D, Braghieri L, Takeda K, Naka Y, Sayer GT, Uriel N, Aaron JG, Montassier E, Demmer RT, Colombo PC. Association of preoperative infections, nasal Staphylococcus aureus colonization and gut microbiota with left ventricular assist device outcomes. Eur J Heart Fail. 2021 Aug;23(8):1404-1415. doi: 10.1002/ejhf.2215. Epub 2021 May 31.
• Background Yuzefpolskaya M, Bohn B, Javaid A, Mondellini GM, Braghieri L, Pinsino A, Onat D, Cagliostro B, Kim A, Takeda K, Naka Y, Farr M, Sayer GT, Uriel N, Nandakumar R, Mohan S, Colombo PC, Demmer RT. Levels of Trimethylamine N-Oxide Remain Elevated Long Term After Left Ventricular Assist Device and Heart Transplantation and Are Independent From Measures of Inflammation and Gut Dysbiosis. Circ Heart Fail. 2021 Jun;14(6):e007909. doi: 10.1161/CIRCHEARTFAILURE.120.007909. Epub 2021 Jun 15.
• Background Staley C, Hamilton MJ, Vaughn BP, Graiziger CT, Newman KM, Kabage AJ, Sadowsky MJ, Khoruts A. Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study. Am J Gastroenterol. 2017 Jun;112(6):940-947. doi: 10.1038/ajg.2017.6. Epub 2017 Feb 14.
• Background Staley C, Kaiser T, Vaughn BP, Graiziger C, Hamilton MJ, Kabage AJ, Khoruts A, Sadowsky MJ. Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat Clostridium difficile Infection. mBio. 2019 Jul 23;10(4):e01586-19. doi: 10.1128/mBio.01586-19.
• Background Khoruts A, Staley C, Sadowsky MJ. Faecal microbiota transplantation for Clostridioides difficile: mechanisms and pharmacology. Nat Rev Gastroenterol Hepatol. 2021 Jan;18(1):67-80. doi: 10.1038/s41575-020-0350-4. Epub 2020 Aug 25.
• Background Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, Khoruts A, Geis E, Maldonado J, McDonough-Means S, Pollard EL, Roux S, Sadowsky MJ, Lipson KS, Sullivan MB, Caporaso JG, Krajmalnik-Brown R. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017 Jan 23;5(1):10. doi: 10.1186/s40168-016-0225-7.
• Background Paramsothy S, Kamm MA, Kaakoush NO, Walsh AJ, van den Bogaerde J, Samuel D, Leong RWL, Connor S, Ng W, Paramsothy R, Xuan W, Lin E, Mitchell HM, Borody TJ. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet. 2017 Mar 25;389(10075):1218-1228. doi: 10.1016/S0140-6736(17)30182-4. Epub 2017 Feb 15.
• Background Agrawal M, Aroniadis OC, Brandt LJ, Kelly C, Freeman S, Surawicz C, Broussard E, Stollman N, Giovanelli A, Smith B, Yen E, Trivedi A, Hubble L, Kao D, Borody T, Finlayson S, Ray A, Smith R. The Long-term Efficacy and Safety of Fecal Microbiota Transplant for Recurrent, Severe, and Complicated Clostridium difficile Infection in 146 Elderly Individuals. J Clin Gastroenterol. 2016 May-Jun;50(5):403-7. doi: 10.1097/MCG.0000000000000410.
• Background Shogbesan O, Poudel DR, Victor S, Jehangir A, Fadahunsi O, Shogbesan G, Donato A. A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplant for Clostridium difficile Infection in Immunocompromised Patients. Can J Gastroenterol Hepatol. 2018 Sep 2;2018:1394379. doi: 10.1155/2018/1394379. eCollection 2018.
• Background Kelly CR, Ihunnah C, Fischer M, Khoruts A, Surawicz C, Afzali A, Aroniadis O, Barto A, Borody T, Giovanelli A, Gordon S, Gluck M, Hohmann EL, Kao D, Kao JY, McQuillen DP, Mellow M, Rank KM, Rao K, Ray A, Schwartz MA, Singh N, Stollman N, Suskind DL, Vindigni SM, Youngster I, Brandt L. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol. 2014 Jul;109(7):1065-71. doi: 10.1038/ajg.2014.133. Epub 2014 Jun 3.
• Background Cheng YW, Alhaffar D, Saha S, Khanna S, Bohm M, Phelps E, Ghabril M, Orman E, Sashidhar S, Rogers N, Xu H, Khoruts A, Vaughn B, Kao D, Wong K, Cammarota G, Ianiro G, Dhere T, Kraft CS, Mehta N, Woodworth MH, Allegretti JR, Nativ L, Marcus J, El-Nachef N, Fischer M. Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis. Clin Gastroenterol Hepatol. 2021 Aug;19(8):1627-1634. doi: 10.1016/j.cgh.2020.06.051. Epub 2020 Jul 6.
• Background Bajaj JS, Kakiyama G, Savidge T, Takei H, Kassam ZA, Fagan A, Gavis EA, Pandak WM, Nittono H, Hylemon PB, Boonma P, Haag A, Heuman DM, Fuchs M, John B, Sikaroodi M, Gillevet PM. Antibiotic-Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant. Hepatology. 2018 Oct;68(4):1549-1558. doi: 10.1002/hep.30037. Epub 2018 Sep 20.
• Background Bajaj JS, Fagan A, Gavis EA, Kassam Z, Sikaroodi M, Gillevet PM. Long-term Outcomes of Fecal Microbiota Transplantation in Patients With Cirrhosis. Gastroenterology. 2019 May;156(6):1921-1923.e3. doi: 10.1053/j.gastro.2019.01.033. Epub 2019 Jan 18. No abstract available.
• Background Bajaj JS, Kassam Z, Fagan A, Gavis EA, Liu E, Cox IJ, Kheradman R, Heuman D, Wang J, Gurry T, Williams R, Sikaroodi M, Fuchs M, Alm E, John B, Thacker LR, Riva A, Smith M, Taylor-Robinson SD, Gillevet PM. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial. Hepatology. 2017 Dec;66(6):1727-1738. doi: 10.1002/hep.29306. Epub 2017 Oct 30.
• Background Bajaj JS, Salzman NH, Acharya C, Sterling RK, White MB, Gavis EA, Fagan A, Hayward M, Holtz ML, Matherly S, Lee H, Osman M, Siddiqui MS, Fuchs M, Puri P, Sikaroodi M, Gillevet PM. Fecal Microbial Transplant Capsules Are Safe in Hepatic Encephalopathy: A Phase 1, Randomized, Placebo-Controlled Trial. Hepatology. 2019 Nov;70(5):1690-1703. doi: 10.1002/hep.30690. Epub 2019 Jun 18.
• Background DeFilipp Z, Bloom PP, Torres Soto M, Mansour MK, Sater MRA, Huntley MH, Turbett S, Chung RT, Chen YB, Hohmann EL. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant. N Engl J Med. 2019 Nov 21;381(21):2043-2050. doi: 10.1056/NEJMoa1910437. Epub 2019 Oct 30.
• Background Robertson SJ, Lemire P, Maughan H, Goethel A, Turpin W, Bedrani L, Guttman DS, Croitoru K, Girardin SE, Philpott DJ. Comparison of Co-housing and Littermate Methods for Microbiota Standardization in Mouse Models. Cell Rep. 2019 May 7;27(6):1910-1919.e2. doi: 10.1016/j.celrep.2019.04.023.
• Background Knights D, Kuczynski J, Charlson ES, Zaneveld J, Mozer MC, Collman RG, Bushman FD, Knight R, Kelley ST. Bayesian community-wide culture-independent microbial source tracking. Nat Methods. 2011 Jul 17;8(9):761-3. doi: 10.1038/nmeth.1650.

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