Mikrobiom: von der Pathophysiologie in die Klinik?

Was ist neu?

Die fest etablierte Indikation der Mikrobiota-Therapie: Clostridioides-difficile-Infektion Die fäkale Mikrobiota-Transplantation (FMT, „Stuhltransplantation“) ist sehr effektiv zur Behandlung der rezidivierenden Clostridioides-difficile-Diarrhöe. Sie ist nun nach den nationalen und internationalen Leitlinien spätestens beim zweiten Rezidiv indiziert. Erste kommerziell hergestellte FMT-Produkte (Rebyota) sind bereits in den USA zugelassen und bei uns im Zulassungsprozess. Kapsel-Präparate aus gereinigten Clostridien-Sporen haben bei der Clostridioides-difficile-Diarrhöe positive Ergebnisse gezeigt und sind ebenfalls im Prozess der Zulassung.

Mikrobiom und Reizdarmsyndrom Beim Reizdarmsyndrom sind die Studien zur FMT teilweise widersprüchlich. Der Verabreichungsweg (Duodenalsonde oder Koloskopie) spielt möglicherweise eine Rolle.

FMT bei chronisch-entzündlichen Darmerkrankungen Bei chronisch-entzündlichen Darmerkrankungen verfestigen sich die Belege, dass FMT bei Colitis ulcerosa wirksam ist, beim Morbus Crohn jedoch nicht.

Das Mikrobiom bei onkologischen Erkrankungen In der Onkologie verfestigen sich Befunde, dass die Mikrobiota die Immunantwort gegen Tumoren und Metastasen beeinflussen kann. Erste Studien zeigen, dass bei manchen Non-Respondern gegenüber einer Checkpoint-Inhibitor-Therapie die Therapieantwort durch FMT von einem Spender mit gutem Therapieresponse wiederhergestellt werden kann.

Abstract

The “microbiome” or the intestinal microbiota is currently in the focus of scientific interest. The number of publications on the topic of the microbiome is increasing every year. In particular, the role of the microbiome in the pathophysiology of various diseases has been studied. Currently it is impossible to have an overview on all new developments with over 25.000 publication in the field per year. However, some key news stand out from this large number of publications. The first microbiota compounds for the therapy of Clostridioides difficile colitis were approved by the FDA last year or are about to be approved. This means that, for the first time, standardized microbiome products are available in addition to fecal microbiota transplantation (FMT) and are finding their way into everyday clinical practice.

Schlüsselwörter

Mikrobiota - Fäkale Mikrobiota - Transplantation - Mikrobiom - Clostridioides difficile Kolitis - chronisch-entzündliche Darmerkrankungen - Dysbiose

Keywords

microbiota - fecal microbiota transplantation - microbiome - Clostridioides difficile colitis - inflammatory bowel disease - dysbiosis

Publication History

Article published online:
02 November 2023

• Literatur

• 1 Shehata E, Parker A, Suzuki T. et al. Microbiomes in physiology: insights into 21st-century global medical challenges. Exp Physiol 2022; 107: 257-264
• 2 Kurt F, Leventhal GE, Spalinger MR. et al. Co-cultivation is a powerful approach to produce a robust functionally designed synthetic consortium as a live biotherapeutic product (LBP). Gut Microbes 2023; 15: 2177486 DOI: 10.1080/19490976.2023.2177486. (PMID: 36794804)
• 3 van Nood E, Vrieze A, Nieuwdorp M. et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013; 368: 407-415 DOI: 10.1056/NEJMoa1205037. (PMID: 23323867)
• 4 Kelly CR, Yen EF, Grinspan AM. et al. Fecal Microbiota Transplantation Is Highly Effective in Real-World Practice: Initial Results From the FMT National Registry. Gastroenterology 2021; 160: 183-192.e3
• 5 US Food and Drug Administration. BLA Approval (30.11.2022). Accessed June 07, 2022 at: https://www.fda.gov/media/163586/download
• 6 Feuerstadt P, Allegretti JR, Khanna S. Practical Use of RBX2660 for the Prevention of Recurrent Clostridioides difficile Infection. Am J Gastroenterol 2023; DOI: 10.14309/ajg.0000000000002195. (PMID: 36695753)
• 7 Orenstein R, Dubberke ER, Khanna S. et al. Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial. BMC Infect Dis 2022; 22: 245
• 8 Khanna S, Assi M, Lee C. et al. Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial with a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection. Drugs 2022; 82: 1527-1538
• 9 Feuerstadt P, Louie TJ, Lashner B. et al. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med 2022; 386: 220-229 DOI: 10.1056/NEJMoa2106516. (PMID: 35045228)
• 10 Rokkas T, Hold GL. A systematic review, pairwise meta-analysis and network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in irritable bowel syndrome. Eur J Gastroenterol Hepatol 2023; 35: 471-479 DOI: 10.1097/MEG.0000000000002519. (PMID: 36719820)
• 11 El-Salhy M, Kristoffersen AB, Valeur J. et al. Long-term effects of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome. Neurogastroenterol Motil 2022; 34: e14200
• 12 Mocanu V, Rajaruban S, Dang J. et al. Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis. J Clin Med 2021; 10: 959 DOI: 10.3390/jcm10050959. (PMID: 33804464)
• 13 Haifer C, Paramsothy S, Kaakoush NO. et al. Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol 2022; 7: 141-151 DOI: 10.1016/S2468-1253(21)00400-3. (PMID: 34863330)
• 14 Tilg H, Adolph TE, Gerner RR. et al. The Intestinal Microbiota in Colorectal Cancer. Cancer Cell 2018; 33: 954-964 DOI: 10.1016/j.ccell.2018.03.004. (PMID: 29657127)
• 15 Elkrief A, Derosa L, Zitvogel L. et al. The intimate relationship between gut microbiota and cancer immunotherapy. Gut Microbes 2019; 10: 424-428
• 16 Davar D, Dzutsev AK, McCulloch JA. et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science 2021; 371: 595-602 DOI: 10.1126/science.abf3363. (PMID: 33542131)
• 17 Baruch EN, Youngster I, Ben-Betzalel G. et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 2021; 371: 602-609 DOI: 10.1126/science.abb5920. (PMID: 33303685)