Treating Obesity and Metabolic Syndrome with Fecal Microbiota Transplantation

Clarisse A Marotz, Amir Zarrinpar, Clarisse A Marotz, Amir Zarrinpar

Abstract

The worldwide prevalence of metabolic syndrome, which includes obesity and its associated diseases, is rising rapidly. The human gut microbiome is recognized as an independent environmental modulator of host metabolic health and disease. Research in animal models has demonstrated that the gut microbiome has the functional capacity to induce or relieve metabolic syndrome. One way to modify the human gut microbiome is by transplanting fecal matter, which contains an abundance of live microorganisms, from a healthy individual to a diseased one in the hopes of alleviating illness. Here we review recent evidence suggesting efficacy of fecal microbiota transplant (FMT) in animal models and humans for the treatment of obesity and its associated metabolic disorders.

Keywords: Fecal microbiota transplant; metabolic syndrome; obesity.

Figures

Figure 1
Figure 1
Fecal Microbiota Transplantation schematic.A) Donor fecal matter is blended with saline solution and pushed through a metal sieve to achieve a homogenous liquid solution. B) Processed fecal microbiota is either delivered via a duodenal tube or colonoscopy. C) Representative data showing metagenomic diversity increases following FMT from lean donor to obese recipient.

References

    1. Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242–249.
    1. Gerard P. Gut microbiota and obesity. Cell Mol Life Sci. 2016;73(1):147–162.
    1. Qin J, Li R, Raes J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65.
    1. Ley RE, Hamady M, Lozupone C. et al. Evolution of mammals and their gut microbes. Science. 2008;320(5883):1647–1651.
    1. Greenblum S, Turnbaugh PJ, Borenstein E. Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease. Proc Natl Acad Sci U S A. 2012;109(2):594–599.
    1. Ley RE, Turnbaugh PJ, Klein S. et al. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444(7122):1022–1023.
    1. Preidis GA, Versalovic J. Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era. Gastroenterology. 2009;136(6):2015–2031.
    1. Kristensen NB, Bryrup T, Allin KH. et al. Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials. Genome medicine. 2016;8(1):52.
    1. van Nood E, Vrieze A, Nieuwdorp M. et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–415.
    1. Zhang F, Luo W, Shi Y. et al. Should we standardize the 1,700-year-old fecal microbiota transplantation? Am J Gastroenterol. 2012;107(11):1755.
    1. Kassam Z, Lee CH, Yuan Y. et al. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013;108(4):500–508.
    1. Vrieze A, Van Nood E, Holleman F. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):913–916.
    1. Di Luccia B, Crescenzo R, Mazzoli A. et al. Rescue of Fructose-Induced Metabolic Syndrome by Antibiotics or Faecal Transplantation in a Rat Model of Obesity. PloS One. 2015;10(8):e0134893.
    1. Backhed F, Ley RE, Sonnenburg JL. et al. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915–1920.
    1. Shen J, Obin MS, Zhao L. et al. The gut microbiota, obesity and insulin resistance. Mol Aspects Med. 2013;34(1):39–58.
    1. Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol. 2013;27(1):73–83.
    1. Matsumoto M, Kibe R, Ooga T. et al. Impact of intestinal microbiota on intestinal luminal metabolome. Scientific reports. 2012;2:233.
    1. Utzschneider KM, Kratz M, Damman CJ. et al. Mechanisms Linking the Gut Microbiome and Glucose Metabolism. J Clin Endocrinol Metab. 2016;101(4):1445–1454.
    1. Turnbaugh PJ, Ley RE, Mahowald MA. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–1031.
    1. Calkin AC, Tontonoz P. Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR. Nature reviews Molecular cell biology. 2012;13(4):213–224.
    1. Sayin SI, Wahlstrom A, Felin J. et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell metabolism. 2013;17(2):225–235.
    1. Zarrinpar A, Loomba R. Review article: the emerging interplay among the gastrointestinal tract, bile acids and incretins in the pathogenesis of diabetes and non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2012;36(10):909–921.
    1. Pols TW, Noriega LG, Nomura M. et al. The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation. J Hepatol. 2011;54(6):1263–1272.
    1. Zhang C, Zhang M, Wang S. et al. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J. 2010;4(2):232–241.
    1. Zarrinpar A, Chaix A, Yooseph S. et al. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell metabolism. 2014;20(6):1006–1017.
    1. Thaiss CA, Zeevi D, Levy M. et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell. 2014;159(3):514–529.
    1. Leone V, Gibbons SM, Martinez K. et al. Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell Host Microbe. 2015;17(5):681–689.
    1. Liang X, Bushman FD, FitzGerald GA. et al. Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock. Proc Natl Acad Sci U S A. 2015;112(33):10479–10484.
    1. Grehan MJ, Borody TJ, Leis SM. et al. Durable alteration of the colonic microbiota by the administration of donor fecal flora. J Clin Gastroenterol. 2010;44(8):551–561.
    1. Lee CH, Steiner T, Petrof EO. et al. Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA. 2016;315(2):142–149.
    1. Hamilton MJ, Weingarden AR, Sadowsky MJ. et al. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(5):761–767.
    1. Cui B, Xu F, Zhang F. et al. Methodology, Not Concept of Fecal Microbiota Transplantation, Affects Clinical Findings. Gastroenterology. 2016;150(1):285–286.
    1. van der Waaij LA, Mesander G, Limburg PC. et al. Direct flow cytometry of anaerobic bacteria in human feces. Cytometry. 1994;16(3):270–279.
    1. Youngster I, Sauk J, Pindar C. et al. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study. Clin Infect Dis. 2014;58(11):1515–1522.
    1. Ridaura VK, Faith JJ, Rey FE. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214.
    1. Borody TJ, Paramsothy S, Agrawal G. Fecal microbiota transplantation: indications, methods, evidence, and future directions. Curr Gastroenterol Rep. 2013;15(8):337.
    1. Nieuwdorp M, Gilijamse PW, Pai N. et al. Role of the microbiome in energy regulation and metabolism. Gastroenterology. 2014;146(6):1525–1533.
    1. Vermeire S, Joossens M, Verbeke K. et al. Donor Species Richness Determines Faecal Microbiota Transplantation Success in Inflammatory Bowel Disease. J Crohns Colitis. 2016;10(4):387–394.
    1. Anderson JL, Edney RJ, Whelan K. et al. Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease. Aliment Pharmacol Ther. 2012;36(6):503–516.
    1. Hawkins AK, O'Doherty KC. "Who owns your poop?": insights regarding the intersection of human microbiome research and the ELSI aspects of biobanking and related studies. BMC Med Genomics. 2011;4:72.
    1. Youngster I, Russell GH, Pindar C. et al. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014;312(17):1772–1778.
    1. Zipursky JS, Sidorsky TI, Freedman CA. et al. Patient attitudes toward the use of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection. Clin Infect Dis. 2012;55(12):1652–1658.
    1. Brandt LJ, Aroniadis OC, Mellow M. et al. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(7):1079–1087.
    1. Kelly CR, Ihunnah C, Fischer M. et al. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol. 2014;109(7):1065–1071.
    1. Baxter M, Colville A. Adverse events in faecal microbiota transplant: a review of the literature. J Hosp Infect. 2016;92(2):117–127.
    1. Kump PK, Grochenig HP, Lackner S. et al. Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis. Inflamm Bowel Dis. 2013;19(10):2155–2165.
    1. Colman RJ, Rubin DT. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis. 2014;8(12):1569–1581.
    1. Gregory JC, Buffa JA, Org E. et al. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290(9):5647–5660.
    1. Alang N, Kelly CR. Weight Gain After Fecal Microbiota Transplantation. Open Forum Infect Dis. 2015;2(1):ofv004.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться