Stool transplant

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A chair transplantation or fecal microbiota transplantation ( FMT ) (also: fecal Mikrobiomtransfer , fecal bacteriotherapy and Fäkaltransplantation ) is the transmission of stool from a healthy donor into the intestine of a sick person by endoscopy or capsules.

The transfer of the intestinal flora from one person to another for therapeutic reasons is described using different terms in the current literature. In the Anglo-Saxon literature, the term fecal microbiota transplantation is often used, which means something like fecal intestinal flora transplantation or fecal bacterial transplantation . It is also customary to simply describe the procedure (for example, Duodenal Infusion of Donor Feces , which means introduction of donor stool into the duodenum ). In the German-language literature there are terms such as fecal therapy, fecal microbiome transfer, stool transplantation, stool transplantation or fecal bacterial therapy.

history

The first ( retrograde ) transmission of the intestinal flora was successfully carried out in 1958 in Denver in a patient with fulminant life-threatening pseudomembranous enterocolitis , but the therapeutic approach was initially not pursued further.

The therapeutic use of stool internally, however, is much older. The German doctor Christian Franz Paullini (1643–1712) describes numerous examples of applications of his time in his textbook Heilsame Dreck-Apotheke , published in 1697 . But also in China of the Dong-jin dynasty in the 4th century, Ge Hong already described an internal use of faeces in an emergency medicine textbook.

This form of treatment attracted attention again in 2013, when the renowned journal The New England Journal of Medicine published an article entitled “Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile ”. While the first attempts were made using a retrograde enema into the large intestine , during the 2013 study antegrade foreign feces were introduced into the small intestine via a nasal tube.

application areas

The transmission of the intestinal flora was investigated, particularly in the case of Clostridium difficile- associated colitis . The approach is that damaged intestinal flora strongly favors relapses, since Clostridium difficile germs can multiply unhindered thanks to the lack of competition from physiological intestinal germs. The “biodiversity” of the stool is significantly reduced in antibiotic-associated colitis compared to normal stool. Convincing results are now available for this application.

In the meantime, however, the effect of a stool transplant is also being investigated on many other diseases that could be related to a pathological disorder of the intestinal flora, a dysbiosis.

execution

In the original application, the stool from a healthy donor is mixed with physiological saline solution and the mixture is roughly filtered. The resulting suspension is introduced into the patient's large intestine through an enema or during a colonoscopy or injected into the duodenum through a duodenal probe .

Capsules are now increasingly being produced. To this end, the donors are initially screened extensively, for which the American FDA published a protocol in 2018. The stool is then liquefied, cleaned, mixed, concentrated and suspended in saline solution containing 40% glycerine . This solution is processed into acid-resistant capsules with a double hydroxy-propyl-methyl-cellulose layer, which can be stored at −90 ° C for up to nine months.

Encapsulation of the fecal microbiome (stored at −20 ° C) is now the procedure of choice.

Clinical studies

Initial overviews of individual case reports showed a success of therapy with stool applied by enema or colonoscopy in 92%. A first randomized, controlled, non-blinded Dutch-Finnish study had to be stopped prematurely because of the clear superiority of stool transplantation. In only 42 older study patients , all of whom had one to nine relapses of Clostridium difficile enterocolitis, 16 patients received a stool transplant using a nasoduodenal tube after a four-day administration of vancomycin and colon cleansing. This therapy was successful in 13 patients (81%) at the first attempt without relapse in the first ten weeks, a second stool transplant was successful in two of the remaining three patients. In the two control groups, however, only three out of thirteen patients (23%) who received vancomycin and colon cleansing were recurrence-free , and only four out of thirteen (31%) patients who received only vancomycin therapy. However, this study was not blinded and excluded patients with immunosuppression, patients in intensive care units, and patients who were receiving other antibiotics for other infections. In this study, almost all patients had diarrhea immediately following the stool transplant (94%), many also had abdominal cramps (31%) and belching (19%). After three hours, all patients were symptom-free. As the disease progressed, 19% developed constipation.

In addition, this technique has already been used several times in patients with inflammatory bowel disease. Another indication could be the treatment of obesity , after studies with mice showed that fat mice lost weight after stool transplantation from thin mice.

Risks

Overall, undesirable side effects rarely occur, especially diverse gastrointestinal disorders, as well as isolated bacteremia and rarely deaths.

In June 2019, the US Food and Drug Administration reported on cases of the transmission of multi-resistant bacteria in clinical FMT applications: two recipients developed invasive bacterial infections after a stool transplantation from an ESBL -producing multi-resistant Escherichia coli pathogen, as a result of which one of the recipients developed died and the other recipient became seriously ill. In both recipients, FMT preparations had been made from stool from the same donor who had not previously been tested for multi-resistant pathogens. The FDA issued a warning about these risks. According to a publication from 2017, colonoscopic application resulted in 1465 cases and two deaths from colon perforation.

The German drug authority BfArM pointed out that it has high safety requirements for applications for the approval of clinical trials with FMT in order to minimize the risk of pathogen transmission. In addition to a comprehensive and multi-stage donor selection and testing, which also includes multi-resistant pathogens, she requests a comprehensive safety report after each FMT transfer in a German test center. Measures can also be imposed, such as tight controls.

literature

Web links

Individual evidence

  1. ↑ a b Clostridial diarrhea: feces through the nose. In: Doctors newspaper online. February 6, 2013, (online) ; last accessed on February 16, 2013.
  2. ↑ MD Agito, A. Atreja, MK Rizk: Fecal microbiota transplantation for recurrent C difficile infection: Ready for prime time? In: Cleve Clin J Med. 80 (2), Feb 2013, pp. 101-108. doi: 10.3949 / ccjm.80a.12110 . PubMed PMID 23376915 .
  3. ↑ CP Kelly: Fecal microbiota transplantation - an old therapy comes of age. In: N Engl J Med. 368 (5), Jan 31, 2013, pp. 474-475. doi: 10.1056 / NEJMe1214816 . Epub 2013 Jan 16. PubMed PMID 23323865 .
  4. ↑ LJ Brandt: American Journal of Gastroenterology Lecture: Intestinal Microbiota and the Role of Fecal Microbiota Transplant (FMT) in Treatment of C. difficile Infection. In: Am J Gastroenterol . 108 (2), Feb 2013, pp. 177-185. doi: 10.1038 / ajg.2012.450 . Epub 2013 Jan 15. PubMed PMID 23318479 .
  5. ^ A b c Els van Nood et al: Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. In: N Engl J Med . 368, 2013, pp. 407-415, online ( memento from January 20, 2013 in the Internet Archive )
  6. ^ Jörg Blech: Medicine - Heilsamer Stuhl . In: Der Spiegel . March 5, 2011; last accessed on February 8, 2013.
  7. ↑ B. Eiseman, W. Silen, GS Bascom, AJ Kauvar: Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. In: Surgery . Volume 44, Number 5, November 1958, pp. 854-859, ISSN  0039-6060 . PMID 13592638 .
  8. ↑ Steven Lehrer: Duodenal Infusion of Feces for Recurrent Clostridium difficile. In: New England Journal of Medicine. Volume 368, Issue 22, May 30, 2013, p. 2144, doi: 10.1056 / NEJMc1303919 .
  9. ↑ Els van Nood, Marcel Dijkgraaf GW, Josbert J. Keller: Duodenal infusion of feces for Recurrent Clostridium difficile. In: New England Journal of Medicine. Volume 368, Issue 22, May 30, 2013, p. 2145, doi: 10.1056 / NEJMc1303919 .
  10. ↑ Martin J. Blaser: Fecal Microbiota Transplantation fo Dysbiosis - Predictable Risks New England Journal of Medicine 2019, Volume 381, Issue 21 of November 21, 2919, pages 2064-2066, DOI: 10.1056 / NEJMe1913807
  11. ^ A b Zachariah DeFilipp, Patricia P. Bloom, Mariam Torres Soto, Michael K. Mansour, Mohamad RA Sater, Miriam H. Huntley, Sarah Turbett, Raymond T. Chung, Yi-Bin Chen, Elizabeth L. Hohmann: Drug-Resistant E. coli Bacteremia Transplanted by Fecal Microbiota Transplant New England Journal of Medicine 2019, Volume 381, Issue 21 November 21, 2019, pages 2043-2050, DOI: 10.1056 / NEJMoa1910437
  12. ↑ Andreas Stallmach and others: Faecal microbiota transfer. Secure indications, donor screening and application forms. In: Deutsches Ärzteblatt. Volume 117, Issue 3, January 17, 2020, pp. 31–38.
  13. ↑ E. Gough, H. Shaikh, AR Manges: Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. In: Clinical Infectious Diseases . Volume 53, Number 10, November 2011, pp. 994-1002, ISSN  1537-6591 . doi: 10.1093 / cid / cir632 . PMID 22002980 . (Review)
  14. ↑ Els van Nood et al: Duodenal infusion of donor feces for recurrent Clostridium difficile. In: The New England Journal of Medicine . Volume 368, Number 5, January 2013, pp. 407-415, ISSN  1533-4406 doi: 10.1056 / NEJMoa1205037 . PMID 23323867 .
  15. ↑ PK Kump et al.: Fecal bacterial therapy (stool transplantation) in therapy-refractory ulcerative colitis - a pilot study. In: Z Gastroenterol. Volume 50, 2012, Article P26. doi: 10.1055 / s-0032-1313865
  16. ↑ Vanessa K. Ridaura et al .: Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice. In: Science. Vol. 341, no.6150, September 6, 2013. ( Online abstract accessed February 17, 2015.)
  17. ↑ Center for Biologics Evaluation and Research: Important Safety Alert Regarding Use of Fecal Microbiota for Transplantation and Risk of Serious Adverse Reactions Due to Transmission of Multi-Drug Resistant Organisms . In: FDA . June 18, 2019 ( fda.gov [accessed June 21, 2019]).
  18. ↑ MN Quraishi et al.: Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. In: Aliment Pharm Ther. Volume 46, 2017, pp. 479-493.
  19. ↑ BfArM - Further drug risks - Risk of transmission of multi-resistant pathogens through fecal microbiota transplantation (FMT, stool transplantation). Retrieved June 21, 2019 .