The hardware method of biomaterial preparation for fecal transplantation

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Abstract

Background: Nowadays fecal transplantation (FT) is considered as a  component of the treatment for a  wide range of disorders, including autoimmune diseases (ulcerative colitis, Crohn's disease, type 1 diabetes mellitus and insulin resistance, multiple sclerosis, psoriasis). High-quality preparation of the biomaterial is a necessary procedure that allows for long-time storage of the prepared fecal transplant at ultralow temperature conditions and it use as needed.

Aim: To optimize the method of preparation of the biomaterial for fecal transplantation and to evaluate its "survival" at different time points under cryopreservation conditions.

Materials and methods: A device for the preparation of donor fecal material for transplantation has been developed and proposed (the Russian Federation patent No. 2659417 from July 2, 2018). Donor fecal material (collected in a  sterile container on the same day of preparation in the morning), the solvent, and glycerol are homogenized automatically in the closed loop device and passed through a disposable filter with attached sterile hemocon container. Freezing at ultralow temperature (cryopreservation at -80 °C) allows for long time storage of this fecal graft. We studied the microbial composition of the obtained native substrate and samples that were cryopreserved at different time points (7 to 365 days).

Results: The proposed original method makes it possible to prepare the biomaterial for storage at a low temperature mode without any contact, in a  closed loop, for subsequent fecal transplantation within 6–12 months. The analysis of the fecal transplant at different time points has shown no qualitative and quantitative differences in the microbial composition between the native donor material and the freshly prepared filtrate. The biomaterial prepared according to the original method is stable for 12 months.

Conclusion: The proposed hardware method for preparing the biomaterial for fecal transplantation is easy to use and allows for the preparation of a  graft with minimal external microbial contamination, in contrast to the conventional method of donor material preparation by filtering fecal matter through gauze or coffee filters with manual assistance.

About the authors

L. R. Shedoeva

Irkutsk Scientific Center of Surgery and Traumatology

Author for correspondence.
Email: cristal608@yandex.ru
ORCID iD: 0000-0002-6525-3522

Liudmila R. Shedoeva – MD, Coloproctologist, Junior Research Fellow, Laboratory of Reconstructive Surgery, Scientific Department of Clinical Surgery 

1 Bortsov Revolyutsii ul., Irkutsk, 664003

Россия

E. Yu. Chashkova

Irkutsk Scientific Center of Surgery and Traumatology

Email: fake@neicon.ru
ORCID iD: 0000-0002-7953-6523

Elena Yu. Chashkova – MD, PhD, Coloproctologist, Leading Research Fellow, Head of Laboratory of Reconstructive Surgery, Scientific Department of Clinical Surgery 

1 Bortsov Revolyutsii ul., Irkutsk, 664003

Россия

O. G. Karnoukhova

Irkutsk State Medical University

Email: fake@neicon.ru

Olga G. Karnoukhova – MD, PhD, Bacteriologist, Associate Professor, Chair of Pathophysiology and Clinical Laboratory Diagnostics 

1 Krasnogo Vosstaniya ul., Irkutsk, 664003

Россия

G. Yu. Kogan

Irkutsk State Medical University

Email: fake@neicon.ru

Galina Yu. Kogan – MD, Bacteriologist, Assistant, Chair of Pathophysiology and Clinical Laboratory Diagnostics 

1 Krasnogo Vosstaniya ul., Irkutsk, 664003

Россия

References

  1. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–15. doi: 10.1056/NEJMoa1205037.
  2. Youngster I, Sauk J, Pindar C, Wilson RG, Kaplan JL, Smith MB, Alm EJ, Gevers D, Russell GH, Hohmann EL. 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– 22. doi: 10.1093/cid/ciu135.
  3. Cammarota G, Masucci L, Ianiro G, Bibbò S, Dinoi G, Costamagna G, Sanguinetti M, Gasbarrini A. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015;41(9):835–43. doi: 10.1111/apt.13144.
  4. Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108(4):478–98; quiz 499. doi: 10.1038/ajg.2013.4.
  5. Sokol H, Galperine T, Kapel N, Bourlioux P, Seksik P, Barbut F, Scanzi J, Chast F, Batista R, Joly F, Joly AC, Collignon A, Guery B, Beaugerie L; French Group of Faecal microbiota Transplantation (FGFT). Faecal microbiota transplantation in recurrent Clostridium difficile infection: Recommendations from the French Group of Faecal microbiota Transplantation. Dig Liver Dis. 2016;48(3):242–7. doi: 10.1016/j.dld.2015.08.017.
  6. Cammarota G, Ianiro G, Tilg H, Rajilić-Stojanović M, Kump P, Satokari R, Sokol H, Arkkila P, Pintus C, Hart A, Segal J, Aloi M, Masucci L, Molinaro A, Scaldaferri F, Gasbarrini G, Lopez-Sanroman A, Link A, de Groot P, de Vos WM, Högenauer C, Malfertheiner P, Mattila E, Milosavljević T, Nieuwdorp M, Sanguinetti M, Simren M, Gasbarrini A; European FMT Working Group. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017;66(4):569–80. doi: 10.1136/gutjnl-2016-313017.
  7. Kelly CR, Kahn S, Kashyap P, Laine L, Rubin D, Atreja A, Moore T, Wu G. Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook. Gastroenterology. 2015;149(1):223–37. doi: 10.1053/j.gastro.2015.05.008.
  8. Шелыгин ЮА, Головенко ОВ, Головенко АО, Сухина МА. Трансплантация фекальной микробиоты – перспективы применения при заболеваниях кишечника (обзор литературы). Колопроктология. 2015;4(54):65–73.
  9. Sood A, Mahajan R, Singh A, Midha V, Mehta V, Narang V, Singh T, Singh Pannu A. Role of Faecal Microbiota Transplantation for Maintenance of Remission in Patients With Ulcerative Colitis: A Pilot Study. J Crohns Colitis. 2019;13(10):1311–7. doi: 10.1093/ecco-jcc/jjz060.
  10. Cui B, Li P, Xu LJ, Peng Z, Zhao Y, Wang H, He Z, Zhang T, Ji G, Wu K, Fan D, Zhang F. Fecal microbiota transplantation is an effective rescue therapy for refractory inflammatory bowel disease. Inflamm Cell Signal. 2015;2:757. doi: 10.14800/ics.757.
  11. Satokari R, Mattila E, Kainulainen V, Arkkila PE. Simple faecal preparation and efficacy of frozen inoculum in faecal microbiota transplantation for recurrent Clostridium difficile infection – an observational cohort study. Aliment Pharmacol Ther. 2015;41(1):46–53. doi: 10.1111/apt.13009.
  12. Orenstein R, Dubberke E, Hardi R, Ray A, Mullane K, Pardi DS, Ramesh MS; PUNCH CD Investigators. Safety and Durability of RBX2660 (Microbiota Suspension) for Recurrent Clostridium difficile Infection: Results of the PUNCH CD Study. Clin Infect Dis. 2016;62(5):596–602. doi: 10.1093/cid/civ938.
  13. Ishikawa D, Sasaki T, Osada T, Kuwahara-Arai K, Haga K, Shibuya T, Hiramatsu K, Watanabe S. Changes in Intestinal Microbiota Following Combination Therapy with Fecal Microbial Transplantation and Antibiotics for Ulcerative Colitis. Inflamm Bowel Dis. 2017;23(1):116– 25. doi: 10.1097/MIB.0000000000000975.
  14. Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, Löwenberg M, van den Brink GR, Mathus-Vliegen EM, de Vos WM, Zoetendal EG, D'Haens GR, Ponsioen CY. Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology. 2015;149(1):110–8.e4. doi: 10.1053/j.gastro.2015.03.045.
  15. Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, Armstrong D, Marshall JK, Kassam Z, Reinisch W, Lee CH. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015;149(1):102–9.e6. doi: 10.1053/j.gastro.2015.04.001.
  16. 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;389(10075):1218–28. doi: 10.1016/S0140-6736(17)30182-4.
  17. Costello SP, Hughes PA, Waters O, Bryant RV, Vincent AD, Blatchford P, Katsikeros R, Makanyanga J, Campaniello MA, Mavrangelos C, Rosewarne CP, Bickley C, Peters C, Schoeman MN, Conlon MA, Roberts-Thomson IC, Andrews JM. Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial. JAMA. 2019;321(2):156–64. doi: 10.1001/jama.2018.20046.
  18. Kump P, Wurm P, Gröchenig HP, Wenzl H, Petritsch W, Halwachs B, Wagner M, Stadlbauer V, Eherer A, Hoffmann KM, Deutschmann A, Reicht G, Reiter L, Slawitsch P, Gorkiewicz G, Högenauer C. The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis. Aliment Pharmacol Ther. 2018;47(1):67–77. doi: 10.1111/apt.14387.
  19. Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(5):761–7. doi: 10.1038/ajg.2011.482.
  20. OpenBiome [Internet]. Available from: http:// www.openbiome.org.
  21. Zhang T, Lu G, Zhao Z, Liu Y, Shen Q, Li P, Chen Y, Yin H, Wang H, Marcella C, Cui B, Cheng L, Ji G, Zhang F. Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening. Protein Cell. 2020;11(4):251–66. doi: 10.1007/s13238-019-00684-8.
  22. Апарцин КА, Кулундуков АА, Чашкова ЕЮ, авторы; ФГБНУ ИНЦХТ, ФГБУН ИНЦ СО РАН, патентообладатели. Устройство для подготовки донорского фекального материала к трансплантации. Пат. 2659417 Рос. Федерация. Опубл. 02.07.2018.
  23. Dupont HL, Jiang ZD, Dupont AW, Utay NS. The intestinal microbiome in human health and disease. Trans Am Clin Climatol Assoc. 2020;131:178–97.
  24. Cammarota G, Ianiro G, Kelly CR, Mullish BH, Allegretti JR, Kassam Z, Putignani L, Fischer M, Keller JJ, Costello SP, Sokol H, Kump P, Satokari R, Kahn SA, Kao D, Arkkila P, Kuijper EJ, Vehreschild MJG, Pintus C, Lopetuso L, Masucci L, Scaldaferri F, Terveer EM, Nieuwdorp M, López-Sanromán A, Kupcinskas J, Hart A, Tilg H, Gasbarrini A. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice. Gut. 2019;68(12):2111–21. doi: 10.1136/gutjnl-2019-319548.
  25. Jiang ZD, Alexander A, Ke S, Valilis EM, Hu S, Li B, DuPont HL. Stability and efficacy of frozen and lyophilized fecal microbiota transplant (FMT) product in a mouse model of Clostridium difficile infection (CDI). Anaerobe. 2017;48:110–4. doi: 10.1016/j.anaerobe.2017.08.003.

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Copyright (c) 2020 Shedoeva L.R., Chashkova E.Y., Karnoukhova O.G., Kogan G.Y.

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