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Current Hepatology Reports
Published in: Current Hepatology Reports 3/2020

Open Access 01-09-2020 | Hepatic Encephalopathy | Management of the Cirrhotic Patient (A Cardenas and P Tandon, Section Editors)

Lessons Learned from Faecal Microbiota Transplantation in Cirrhosis

Authors: Grace B. Hatton, Shaolu Ran, Thomas H. Tranah, Debbie L. Shawcross

Published in: Current Hepatology Reports | Issue 3/2020

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Abstract

Purpose of Review

We examine recent developments in the treatment of cirrhosis by gut microbiome manipulation specifically focusing on the phase 1 safety and feasibility trials of faecal microbiota transplantation (FMT). We interrogate the published data so far on its feasibility, safety and efficacy.

Recent Findings

A large number of trials have demonstrated the efficacy of FMT in treating recurrent Clostridium difficile infection which is now considered standard of care. In cirrhosis, FMT is still being evaluated and there are a number of clinical trials underway. There are two phase 1 pilot safety studies that have been published with promising findings. However, the importance of rigorously testing donor stool for the presence of multi-drug resistant species has been highlighted and lessons have been learned.

Summary

For those patients with cirrhosis, replacing an unhealthy gut microbiome with a healthy one offers a promising antibiotic-free treatment that may reduce bacterial translocation and endotoxemia.
Literature
1.
Lozano R, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 (vol 380, pg 2095, 2012). Lancet. 2013;381(9867):628.
2.
Williams R, Aspinall R, Bellis M, Camps-Walsh G, Cramp M, Dhawan A, et al. Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis. Lancet. 2014;384(9958):1953–97.CrossRefPubMed
3.
Borzio M, Salerno F, Piantoni L, Cazzaniga M, Angeli P, Bissoli F, et al. Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study. Dig Liver Dis. 2001;33(1):41–8.PubMed
4.
Jalan R, Fernandez J, Wiest R, Schnabl B, Moreau R, Angeli P, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol. 2014;60(6):1310–24.CrossRefPubMed
5.
Shawcross DL, Austin MJ, Abeles RD, McPhail MJW, Yeoman AD, Taylor NJ, et al. The impact of organ dysfunction in cirrhosis: survival at a cost? J Hepatol. 2012;56(5):1054–62.PubMed
6.
Bajaj JS, Heuman DM, Hylemon PB, Sanyal AJ, White MB, Monteith P, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol. 2014;60(5):940–7.PubMed
7.
Bishehsari F, Magno E, Swanson G, Desai V, Voigt RM, Forsyth CB, et al. Alcohol and gut-derived inflammation. Alcohol Research-Current Reviews. 2017;38(2):163–71.PubMedPubMedCentral
8.
Albillos A, Lario M, Alvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014;61(6):1385–96.PubMed
9.
O'Brien AJ, et al. Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E-2. Nat Med. 2014;20(5):522–7.
10.
Fernandez J, et al. Multidrug-resistant bacterial infections in patients with decompensated cirrhosis and with acute-on-chronic liver failure in Europe. J Hepatol. 2019;70(3):398–411.CrossRefPubMed
11.
Volk ML, Tocco RS, Bazick J, Rakoski MO, Lok AS. Hospital readmissions among patients with decompensated cirrhosis. Am J Gastroenterol. 2012;107(2):247–52.CrossRefPubMed
12.
Fernandez J, et al. Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatology. 2012;55(5):1551–61.CrossRefPubMed
13.
Huttenhower C, et al. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14.CrossRef
14.
De Cruz P, et al. Characterization of the gastrointestinal microbiota in health and inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(2):372–90.CrossRefPubMed
15.
Valdes AM, et al. Role of the gut microbiota in nutrition and health. Br Med J. 2018;361.
16.
Rajilic-Stojanovic M, et al. Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm Bowel Dis. 2013;19(3):481–8.CrossRefPubMed
17.
Bajaj JS, Betrapally NS, Hylemon PB, Heuman DM, Daita K, White MB, et al. Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy. Hepatology. 2015;62(4):1260–71.CrossRefPubMed
18.
Francino MP. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front Microbiol. 2016;6.
19.
• Bajaj, J.S., et al., Fungal dysbiosis in cirrhosis. Gut, 2018. 67(6): p. 1146-1154. This is the first study which characterises the presence of fungal dysbiosis as being important in determiming outcomes in cirrhosis.
20.
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–63.PubMed
21.
Cotillard A, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500:585–8.PubMed
22.
Singh RK, Chang HW, Yan D, Lee KM, Ucmak D, Wong K, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15(1):73.PubMedPubMedCentral
23.
Islam KB, et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011;141(5):1773–81.PubMed
24.
Yokota A, Fukiya S, Islam KBMS, Ooka T, Ogura Y, Hayashi T, et al. Is bile acid a determinant of the gut microbiota on a high-fat diet? Gut Microbiobes. 2012;3(5):455–9.
25.
Kastorini CM, Milionis HJ, Esposito K, Giugliano D, Goudevenos JA, Panagiotakos DB. The effect of Mediterranean diet on metabolic syndrome and its components: a meta-analysis of 50 studies and 534,906 individuals. J Am Coll Cardiol. 2011;57(11):1299–313.PubMed
26.
Anania C, Perla FM, Olivero F, Pacifico L, Chiesa C. Mediterranean diet and nonalcoholic fatty liver disease. World J Gastroenterol. 2018;24(19):2083–94.PubMedPubMedCentral
27.
•• Bajaj JS et al., Diet affects gut microbiota and modulates hospitalisation risk differentially in an international cirrhosis cohort. Hepatology, 2018. 68(1): p. 234-247. This is an important study which shows how important diet is in patients with cirrhosis in determining outcomes. The Mediterranean diet is particularly beneficial.
28.
Fredua-Agyeman, M. and S. Gaisford, Assessing inhibitory activity of probiotic culture supernatants against Pseudomonas aeruginosa: a comparative methodology between agar diffusion, broth culture and microcalorimetry. World Journal of Microbiology & Biotechnology, 2019. 35(3).
29.
Dodoo CC, Stapleton P, Basit AW, Gaisford S. Use of a water-based probiotic to treat common gut pathogens. Int J Pharm. 2019;556:136–41.PubMed
30.
Ritchie, M.L. and T.N. Romanuk, A meta-analysis of probiotic efficacy for gastrointestinal diseases. PLoS One, 2012. 7(4).
31.
Lee, H.L., et al., Targeted approaches for in situ gut microbiome manipulation. Genes, 2018. 9(7).
32.
McLoughlin RF, et al. Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis. Am J Clin Nutr. 2017;106(3):930–45.PubMed
33.
Saab S, Suraweera D, Au J, Saab EG, Alper TS, Tong MJ. Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials. Liver Int. 2016;36(7):986–93.CrossRefPubMed
34.
Ma YY, Li L, Yu CH, Shen Z, Chen LH, Li YM. Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenterol. 2013;19(40):6911–8.CrossRefPubMedPubMedCentral
35.
Bajaj, J.S., et al., Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy. PLoS One, 2013. 8(4).
36.
• Hudson, M., et al., The impact of rifaximin-alpha on the hospital resource use associated with the management of patients with hepatic encephalopathy: a retrospective observational study (IMPRESS). Frontline Gastroenterology, 2017. 8(4): p. 243-251. This study showed how manipulation of the gut microbiome with a non-absorbable antibiotic could represent significant cost saving to the healthcare system.
37.
•• Salehi, S., et al., Rifaximin reduces the incidence of spontaneous bacterial peritonitis, variceal bleeding and all-cause admissions in patients on the liver transplant waiting list. Alimentary Pharmacology & Therapeutics, 2019. 50(4): p. 435-441. This retrospective study showed for the first time that manipulation of the gut microbiome with rifaximin could reduce all cirrhotic decompensating events and reduce all-cause admissions.
38.
Esfeh JM, et al. Impact of pretransplant rifaximin therapy on post-liver transplant infections. Am J Transplant. 2012;12:209–10.
39.
•• Chang, J.Y., et al., Emergence of rifampin-resistant staphylococci after rifaximin administration in cirrhotic patients. Plos One, 2017. 12(10). This study highlighted the very real concern that even short-term rifaximin use could induce antimicrobial resistance in cirrhotic populations.
40.
Eiseman B, et al. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44(5):854–9.PubMed
41.
El-Salhy, M., et al., Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut, 2019: p. gutjnl-2019-319630.
42.
Anderson JL, Edney RJ, Whelan K. Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease. Aliment Pharmacol Ther. 2012;36(6):503–16.PubMed
43.
Vrieze A, Van Nood E, Holleman F. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome (vol 143, pg 913, 2012). Gastroenterology. 2013;144(1):250.
44.
Mullish BH, Quraishi MN, Segal JP, McCune VL, Baxter M, Marsden GL, et al. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut. 2018;67(11):1920–41.PubMed
45.
• Wilson, B.C., Vatanen T., Cutfield W.S., O’Sullivan J.M., The super-donor phenomenon in fecal microbiota transplantation Front Cell Infect Microbiol, 2019. 9: p. 2. This study shows that not all FMT donors are equal and some donors may be better than others.
46.
•• Bajaj JS, et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatology, 2017. 66(6): p. 1727-1738. This was the first published FMT pilot study in patients with cirrhosis showing it to be safe and potentially efficacious. .
47.
•• Bajaj, J.S., et al., Antibiotic-associated disruption of microbiota composition and function in cirrhosis is restored by fecal transplant. Hepatology, 2018. 68(4): p. 1549–1558. This adjunct manuscript to the study in ref. 46 showed that FMT has the potential to restore antibiotic-induced gut dysbiosis in cirrhosis.
48.
•• Bajaj, J.S., et al., Long-term outcomes of fecal microbiota transplantation in patients with cirrhosis. Gastroenterology, 2019. 156(6): p. 1921–1923.e3. This follow-up study showed that FMT remains safe at 15 months post FMT in cirrhosis.
49.
•• Liu, R.P., et al., Neuroinflammation in murine cirrhosis is dependent on the gut microbiome and is attenuated by fecal transplant. Hepatology, 2020. 71(2): p. 611-626. This seminal study showed that FMT given to patients with cirrhosis may reduce cerebral inflammation.
50.
Moss EL, Falconer SB, Tkachenko E, Wang M, Systrom H, Mahabamunuge J, et al. Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients. PLoS One. 2017;12(8):e0182585.CrossRefPubMedPubMedCentral
51.
•• Bajaj, J.S., et al., Fecal microbial transplant capsules are safe in hepatic encephalopathy: a phase 1, randomized, placebo-controlled trial. Hepatology, 2019. 70(5): p. 1690-1703. This phase 1 study showed for the first time that encapsulated FMT is safe in cirrhosis and has efficacy. These findings now need to be confirmed in large-scale randomised clinical trials.
52.
•• Duan, Y., et al., Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature, 2019. 575(7783): p. 505-511. This ground-breaking study suggested that manipulating the gut microbiome using a phage therapy may be able to reduce liver injury.
53.
Kootte, R.S., et al., Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metabolism, 2017. 26(4): p. 611-+.
54.
Mizuno S, Masaoka T, Naganuma M, Kishimoto T, Kitazawa M, Kurokawa S, et al. Bifidobacterium-rich fecal donor may be a positive predictor for successful fecal microbiota transplantation in patients with irritable bowel syndrome. Digestion. 2017;96(1):29–38.CrossRefPubMed
55.
Broecker, F., et al., Long-term changes of bacterial and viral compositions in the intestine of a recovered Clostridium difficile patient after fecal microbiota transplantation. Cold Spring Harbor Molecular Case Studies, 2016. 2(1).
56.
Moayyedi, P., et al., Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology, 2015. 149(1): p. 102−+.
57.
Anand R, Song Y, Garg S, Girotra M, Sinha A, Sivaraman A, et al. Effect of aging on the composition of fecal microbiota in donors for FMT and its impact on clinical outcomes. Dig Dis Sci. 2017;62(4):1002–8.CrossRefPubMed
58.
DeFilipp M.D et al., Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N Engl J Med, 2019. 381: p. 2043–2050.
59.
Albillos A, de Gottardi A, Rescigno M. The gut-liver axis in liver disease: pathophysiological basis for therapy. J Hepatol. 2020;72(3):558–77.CrossRefPubMed
60.
Santiago-Rodriguez, T.M. and E.B. Hollister, Human virome and disease: high-throughput sequencing for virus discovery, identification of phage-bacteria dysbiosis and development of therapeutic approaches with emphasis on the human gut. Viruses, 2019. 11(7).
61.
Woodhouse, C.A., et al., PROFIT, a PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis: study protocol for a single-blinded trial. BMJ Open, 2019. 9(2).
Metadata
Title
Lessons Learned from Faecal Microbiota Transplantation in Cirrhosis
Authors
Grace B. Hatton
Shaolu Ran
Thomas H. Tranah
Debbie L. Shawcross
Publication date
01-09-2020
Publisher
Springer US
Published in
Current Hepatology Reports / Issue 3/2020
Electronic ISSN: 2195-9595
DOI
https://doi.org/10.1007/s11901-020-00520-2

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