Fecal Microbiota Transplant in Cirrhosis Reduces Gut Microbial Antibiotic Resistance Genes: Analysis of Two Trials.


Journal

Hepatology communications
ISSN: 2471-254X
Titre abrégé: Hepatol Commun
Pays: United States
ID NLM: 101695860

Informations de publication

Date de publication:
02 2021
Historique:
received: 16 09 2020
revised: 21 10 2020
accepted: 22 10 2020
entrez: 8 2 2021
pubmed: 9 2 2021
medline: 9 2 2021
Statut: epublish

Résumé

Antibiotic resistance leads to poor outcomes in cirrhosis. Fecal microbiota transplant (FMT) is associated with reduction in antibiotic resistance gene (ARG) burden in patients without cirrhosis; however, the impact in cirrhosis is unclear. We aimed to study the effect of capsule and enema FMT on ARG abundance in fecal samples, which were collected during two published FMT trials in patients with cirrhosis on rifaximin, lactulose, and proton pump inhibitors. ARGs were identified using metagenomics and mapped against the Comprehensive Antibiotic Resistance Database. Changes in ARG abundance were studied within/between groups. The capsule FMT trial involved a one-time FMT or placebo capsule administration with stool collection at baseline and week 4 postintervention. Antibiotics+enema FMT included preprocedure antibiotics followed by FMT enema versus standard-of-care (SOC). Stool was collected at baseline, postantibiotics, and day 7/15 postintervention. Both trials included 20 patients each. There was no safety/infection signal linked to FMT. In the capsule trial, beta-lactamase (OXY/LEN) expression decreased post-FMT versus baseline. Compared to placebo, patients who were post-FMT had lower abundance of vancomycin (VanH), beta-lactamase (ACT), and rifamycin ARGs; the latter was associated with cognitive improvement. No changes were seen within patients treated with placebo. In the antibiotics+enema trial for postantibiotics at day 7 versus baseline, there was an increase in vancomycin and beta-lactamase ARGs, which decreased at day 15. However, quinolone resistance increased at day 15 versus baseline. Between SOC and FMT, day 7 had largely lower ARG (CfxA beta-lactamase, VanW, and VanX) that continued at day 15 (cepA beta-lactamase, VanW). No changes were seen within the SOC group.

Identifiants

pubmed: 33553973
doi: 10.1002/hep4.1639
pii: 02009842-202102000-00011
pmc: PMC7850310
doi:

Substances chimiques

Anti-Bacterial Agents 0
Proton Pump Inhibitors 0
Lactulose 4618-18-2
Rifaximin L36O5T016N

Types de publication

Clinical Trial, Phase I Journal Article Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Pagination

258-271

Subventions

Organisme : NCATS NIH HHS
ID : R21 TR002024
Pays : United States
Organisme : NCATS NIH HHS
ID : R21 TR003095
Pays : United States

Informations de copyright

© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.

Références

Fernandez J, Prado V, Trebicka J, Amoros A, Gustot T, Wiest R, et al.; European Foundation for the Study of Chronic Liver Failure (EF‐Clif) . Multidrug‐resistant bacterial infections in patients with decompensated cirrhosis and with acute‐on‐chronic liver failure in Europe. J Hepatol 2019;70:398‐411.
Millan B, Park H, Hotte N, Mathieu O, Burguiere P, Tompkins TA, et al. Fecal microbial transplants reduce antibiotic‐resistant genes in patients with recurrent Clostridium difficile infection. Clin Infect Dis 2016;62:1479‐1486.
Bajaj JS, Salzman NH, Acharya C, Sterling RK, White MB, Gavis EA, et al. Fecal microbial transplant capsules are safe in hepatic encephalopathy: a phase 1, randomized, placebo‐controlled trial. Hepatology 2019;70:1690‐1703.
Bajaj JS, Kassam Z, Fagan A, Gavis EA, Liu E, Cox IJ, et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatology 2017;66:1727‐1738.
Martin M. Cutadapt removes adapter sequences from high‐throughput sequencing reads. Embnet.J 2011;17. https://doi.org/10.14806/ej.17.1.200 .
doi: 10.14806/ej.17.1.200
O'Leary NA, Wright MW, Brister JR, Ciufo S, Haddad D, McVeigh R, et al. Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res 2016;44:D733‐D745.
Al‐Ghalith G, Knights D. BURST enables optimal exhaustive DNA alignment for big data. Zenodo 2017; https://doi.org/10.5281/zenodo.806850 .
doi: 10.5281/zenodo.806850
Jia B, Raphenya AR, Alcock B, Waglechner N, Guo P, Tsang KK, et al. CARD 2017: expansion and model‐centric curation of the comprehensive antibiotic resistance database. Nucleic Acids Res 2017;45:D566‐D573.
Shamsaddini A, Dadkhah K, Gillevet PM. BiomMiner: an advanced exploratory microbiome analysis and visualization pipeline. PLoS One 2020;15:e0234860.
White JR, Nagarajan N, Pop M. Statistical methods for detecting differentially abundant features in clinical metagenomic samples. PLoS Comput Biol 2009;5:e1000352.
Piano S, Singh V, Caraceni P, Maiwall R, Alessandria C, Fernandez J, et al.; International Club of Ascites Global Study Group . Epidemiology and effects of bacterial infections in patients with cirrhosis worldwide. Gastroenterology 2019;156:1368‐1380.e1310.
Bajaj JS, O'Leary JG, Tandon P, Wong F, Garcia‐Tsao G, Kamath PS, et al. Nosocomial infections are frequent and negatively impact outcomes in hospitalized patients with cirrhosis. Am J Gastroenterol 2019;114:1091‐1100.
Chen Y, Guo J, Qian G, Fang D, Shi D, Guo L, et al. Gut dysbiosis in acute‐on‐chronic liver failure and its predictive value for mortality. J Gastroenterol Hepatol 2015;30:1429‐1437.
Bajaj JS, Vargas HE, Reddy KR, Lai JC, O'Leary JG, Tandon P, et al. Association between intestinal microbiota collected at hospital admission and outcomes of patients with cirrhosis. Clin Gastroenterol Hepatol 2019;17:756‐765.e753.
Sung CM, Lin YF, Chen KF, Ke HM, Huang HY, Gong YN, et al. Predicting Clinical Outcomes of Cirrhosis Patients With Hepatic Encephalopathy From the Fecal Microbiome. Cell Mol Gastroenterol Hepatol 2019;8:301‐318.e302.
Cheng YW, Alhaffar D, Saha S, Khanna S, Bohm M, Phelps E, et al. Fecal microbiota transplantation is safe and effective in patients with Clostridioides difficile infection and cirrhosis. Clin Gastroenterol Hepatol 2020; https://doi.org/10.1016/j.cgh.2020.06.051 .
doi: 10.1016/j.cgh.2020.06.051
Pringle PL, Soto MT, Chung RT, Hohmann E. Patients with cirrhosis require more fecal microbiota capsules to cure refractory and recurrent Clostridium difficile infections. Clin Gastroenterol Hepatol 2019;17:791‐793.
DeFilipp Z, Bloom PP, Torres Soto M, Mansour MK, Sater MRA, Huntley MH, et al. Drug‐resistant E. coli bacteremia transmitted by fecal microbiota transplant. N Engl J Med 2019;381:2043‐2050.
Saha S, Tariq R, Tosh PK, Pardi DS, Khanna S. Faecal microbiota transplantation for eradicating carriage of multidrug‐resistant organisms: a systematic review. Clin Microbiol Infect 2019;25:958‐963.
Millan B, Park H, Hotte N, Mathieu O, Burguiere P, Tompkins TA, et al. Fecal microbial transplants reduce antibiotic‐resistant genes in patients with recurrent Clostridium difficile infection. Clin Infect Dis 2016;62:1479‐1486.
Jouhten H, Mattila E, Arkkila P, Satokari R. Reduction of antibiotic resistance genes in intestinal microbiota of patients with recurrent Clostridium difficile infection after fecal microbiota transplantation. Clin Infect Dis 2016;63:710‐711.
Puchter L, Chaberny IF, Schwab F, Vonberg RP, Bange FC, Ebadi E. Economic burden of nosocomial infections caused by vancomycin‐resistant enterococci. Antimicrob Resist Infect Control 2018;7:1.
Barger M, Blodget E, Pena S, Mack W, Fong TL. VRE in cirrhotic patients. BMC Infect Dis 2019;19:711.
Rampelli S, Schnorr SL, Consolandi C, Turroni S, Severgnini M, Peano C, et al. Metagenome sequencing of the Hadza hunter‐gatherer gut microbiota. Curr Biol 2015;25:1682‐1693.
Binta B, Patel M. Detection of cfxA2, cfxA3, and cfxA6 genes in beta‐lactamase producing oral anaerobes. J Appl Oral Sci 2016;24:142‐147.
Bajaj JS, Acharya C, Fagan A, White MB, Gavis E, Heuman DM, et al. Proton pump inhibitor initiation and withdrawal affects gut microbiota and readmission risk in cirrhosis. Am J Gastroenterol 2018;113:1177‐1186.
Horvath A, Rainer F, Bashir M, Leber B, Schmerboeck B, Klymiuk I, et al. Biomarkers for oralization during long‐term proton pump inhibitor therapy predict survival in cirrhosis. Sci Rep 2019;9:12000.
Olsen JE, Christensen H, Aarestrup FM. Diversity and evolution of blaZ from Staphylococcus aureus and coagulase‐negative staphylococci. J Antimicrob Chemother 2006;57:450‐460.
Miller WR, Munita JM, Arias CA. Mechanisms of antibiotic resistance in enterococci. Expert Rev Anti Infect Ther 2014;12:1221‐1236.
Bajaj JS, Kakiyama G, Savidge T, Takei H, Kassam ZA, Fagan A, et al. Antibiotic‐associated disruption of microbiota composition and function in cirrhosis is restored by fecal transplant. Hepatology 2018;68:1549‐1558.
Hatton GB, Ran S, Tranah TH, Shawcross DL. Lessons learned from faecal microbiota transplantation in cirrhosis. Curr Hepatol Rep 2020;19:159‐167.
Gupta CL, Tiwari RK, Cytryn E. Platforms for elucidating antibiotic resistance in single genomes and complex metagenomes. Environ Int 2020;138:105667.
Penders J, Stobberingh EE, Savelkoul PH, Wolffs PF. The human microbiome as a reservoir of antimicrobial resistance. Front Microbiol 2013;4:87.
Gosalbes MJ, Vazquez‐Castellanos JF, Angebault C, Woerther PL, Ruppe E, Ferrus ML, et al. Carriage of enterobacteria producing extended‐spectrum beta‐lactamases and composition of the gut microbiota in an Amerindian community. Antimicrob Agents Chemother 2015;60:507‐514.
Gorrie CL, Mirceta M, Wick RR, Edwards DJ, Thomson NR, Strugnell RA, et al. Gastrointestinal carriage is a major reservoir of Klebsiella pneumoniae infection in intensive care patients. Clin Infect Dis 2017;65:208‐215.
Gargiullo L, Del Chierico F, D'Argenio P, Putignani L. Gut microbiota modulation for multidrug‐resistant organism decolonization: present and future perspectives. Front Microbiol 2019;10:1704.
Patriarca F, Cigana C, Massimo D, Lazzarotto D, Geromin A, Isola M, et al. Risk factors and outcomes of infections by multidrug‐resistant gram‐negative bacteria in patients undergoing hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2017;23:333‐339.
Tranah TH, Vijay GK, Ryan JM, Shawcross DL. Systemic inflammation and ammonia in hepatic encephalopathy. Metab Brain Dis 2013;28:1‐5.
Piano S, Brocca A, Mareso S, Angeli P. Infections complicating cirrhosis. Liver Int 2018;38(Suppl. 1):126‐133.

Auteurs

Jasmohan S Bajaj (JS)

Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Central Virginia Veterans Healthcare SystemRichmondVAUSA.

Amirhossein Shamsaddini (A)

Microbiome Analysis CenterGeorge Mason UniversityManassasVAUSA.

Andrew Fagan (A)

Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Central Virginia Veterans Healthcare SystemRichmondVAUSA.

Richard K Sterling (RK)

Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Central Virginia Veterans Healthcare SystemRichmondVAUSA.

Edith Gavis (E)

Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Central Virginia Veterans Healthcare SystemRichmondVAUSA.

Alexander Khoruts (A)

Gastroenterology, Hepatology, and NutritionBiotechnology Institute University of MinnesotaMinneapolisMNUSA.

Michael Fuchs (M)

Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Central Virginia Veterans Healthcare SystemRichmondVAUSA.

Hannah Lee (H)

Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Central Virginia Veterans Healthcare SystemRichmondVAUSA.

Masoumeh Sikaroodi (M)

Microbiome Analysis CenterGeorge Mason UniversityManassasVAUSA.

Patrick M Gillevet (PM)

Microbiome Analysis CenterGeorge Mason UniversityManassasVAUSA.

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