Wie advies wilt over hoe het microbioom te verbeteren zou contact op kunnen nemen met deze website: Www.microbiome-Center.nl Voor zowel artsen als individuele burgers staat een groep van artsen en wetenschappers klaar om u een persoonlijk advies te geven
7 september 2022: Bron: Medisch Contact en Science Translational Medicine
Uit onderzoek van wetenschappers van het UMCG blijkt dat hoe meer de darmflora (darmmicrobiota) van transplantatiepatiënten van vaste organen, zoals niertransplantaties en levertransplantaties, afwijkt van de darmflora van gezonde mensen hoe groter de kans is dat deze patiënten overlijden gerelateerd aan de transplantatie.
Het is al langer bekend dat de darmflora (darmmicrobiota) een grote rol speelt in ons immuunsysteem en ook bij stamceltransplantaties en beenmergtransplantaties een rol speelt in de kansen op succes van de transplantatie. Op basis daarvan onderzochten wetenschappers van het UMCG fecale monsters van patiënten die een niertransplantatie of levertransplantatie hadden ondergaan en vergeleken dat met fecale monsters van een controlegroep van gezonde mensen die overeen kwamen qua leeftijd en geslacht en lichaamsgewicht o.a.
Hun belangrijkste conclusie die uit het onderzoek kwam was dat de darmflora van patiënten die een niertransplantatie of levertransplantatie hadden ondergaan na een nier- of levertransplantatie veel minder divers en anders van samenstelling waren wat betreft de bacteriën in vergelijking met de controlegroep. De onderzoekers zagen een toename van ongezonde soorten bacteriën en een verhoogde prevalentie en diversiteit van antibioticaresistentiegenen en virulentiefactoren. Deze veranderde darmflora werd zelfs gezien tot 20 jaar na de transplantatie had plaatsgevonden. Het gebruik van immuunonderdrukkende medicijnen en antibiotica speelde daarin een grote rol.
De wetenschappers stellen in hun conclusie dat artsen zich voordat de transplantatie gaat plaatsvinden zij zich eerst zouden moeten richten op verbetering van de diversiteit en samenstelling van de darmflora (darmmicrobiota).
Het volledige studierapport is gepubliceerd in Science Translational Medicine en gratis in te zien of te downloaden. Klik op de titel voor het studierapport:
Gut microbiome dysbiosis is associated with increased mortality after solid organ transplantation
Damaging dysbiosis
Reduced gut microbial diversity after allogeneic stem cell transplantation has been associated with decreased survival, but the role of the gut microbiome after solid organ transplantation is not as well studied. Here, Swarte and colleagues studied dysbiosis of the gut microbiome in a large cohort of individuals with end-stage liver or kidney disease before and after organ transplantation. Transplant recipients suffered from gut dysbiosis, with lower diversity and increased abundance of unhealthy species, virulence factors, and antibiotic resistance genes. Furthermore, immunosuppressive drug use was associated with dysbiosis, and increased dysbiosis was associated with increased mortality after transplantation. These results suggest that microbiome-targeted interventions could potentially affect outcomes after solid organ transplantation.
Abstract
Organ transplantation is a life-saving treatment for patients with end-stage disease, but survival rates after transplantation vary considerably. There is now increasing evidence that the gut microbiome is linked to the survival of patients undergoing hematopoietic cell transplant, yet little is known about the role of the gut microbiome in solid organ transplantation. We analyzed 1370 fecal samples from 415 liver and 672 renal transplant recipients using shotgun metagenomic sequencing to assess microbial taxonomy, metabolic pathways, antibiotic resistance genes, and virulence factors. To quantify taxonomic and metabolic dysbiosis, we also analyzed 1183 age-, sex-, and body mass index–matched controls from the same population. In addition, a subset of 78 renal transplant recipients was followed longitudinally from pretransplantation to 24 months after transplantation. Our data showed that both liver and kidney transplant recipients suffered from gut dysbiosis, including lower microbial diversity, increased abundance of unhealthy microbial species, decreased abundance of important metabolic pathways, and increased prevalence and diversity of antibiotic resistance genes and virulence factors. These changes were found to persist up to 20 years after transplantation. Last, we demonstrated that the use of immunosuppressive drugs was associated with the observed dysbiosis and that the extent of dysbiosis was associated with increased mortality after transplantation. This study represents a step toward potential microbiome-targeted interventions that might influence the outcomes of recipients of solid organ transplantation.
Acknowledgments
We wish to acknowledge the services of the Lifelines Cohort Study, the contributing research centers delivering data to Lifelines, and all the study participants. The Lifelines Biobank initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare, and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG the Netherlands), University of Groningen, and the Northern Provinces of the Netherlands. We would like to thank the Center for Information Technology of the University of Groningen (RUG) for support and for providing access to the Peregrine high-performance computing cluster and the Genomic Coordination Center (UMCG and RUG) for support and for providing access to Calculon and Boxy high-performance computing clusters. Metagenomics library preparation and sequencing was done at Novogene. We would like to thank S. A. Mayle for the graphical illustrations used in this study. We also thank K. Mc Intyre for English and content editing. Last, we would like to thank all TransplantLines investigators who were not coauthors of the current manuscript: C. Annema, F. A. J. A. Bodewes, M. T. de Boer, K. Damman, M. H. de Borst, A. Diepstra, G. Dijkstra, M. E. Erasmus, C. T. Gan, E. Hak, B. G. Hepkema, F. Klont, H. G. D. Leuvenink, W. S. Lexmond, H. G. M. Niesters, L. J. van Pelt, R. A. Pol, A. V. Ranchor, M. J. Siebelink, R. J. H. J. A. Slart, D. J. Touw, M. C. van den Heuvel, C. van Leer-Buter, M. van Londen, E. A. M. Verschuuren, and M. J. Vos.
Funding: Sequencing of the Lifelines cohort and the liver part of the TransplantLines cohort was funded by a grant from the CardioVasculair Onderzoek Nederland grant (CVON 2012-03) to M.R.H.-F., J.F., and A.Z. Sequencing of the kidney part of the TransplantLines cohort was funded by a grant from the Dutch NWO/TTW/DSM partnership program Animal Nutrition and Health (project number 14939) to S.J.L.B. R.G. was supported by the collaborative TIMID project (LSHM18057-SGF) financed by the PPP allowance made available by Top Sector Life Sciences & Health to Samenwerkende Gezondheidsfondsen (SGF) to stimulate public-private partnerships and cofinancing by health foundations that are part of the SGF. R.K.W. is supported by the Seerave Foundation. A.Z. is supported by the ERC Starting Grant 715772, Netherlands Organization for Scientific Research NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and the NWO Gravitation grant ExposomeNL 024.004.017. V.E.d.M. is supported by Netherlands Organization for Scientific Research NWO-VENI grant 09150161810030. J.F. is supported by NWO Gravitation Netherlands Organ-on-Chip Initiative (024.003.001), the ERC Consolidator grant 101001678, and the Netherlands Heart Foundation CVON grant 2018-27. C.W. is further supported by a European Research Council (ERC) advanced grant (ERC-671274) and an NWO Spinoza award (NWO SPI 92-266).
Author contributions: J.C.S., Y.L., and S.H. drafted the first version of the manuscript. J.C.S., J.R.B., and R.K.W. wrote and finalized subsequent versions of the manuscript. All authors critically revised and approved the final version of the manuscript. J.C.S., S.H., J.R.B., and R.G. performed the statistical analyses. R.G. designed and implemented metagenomic data analysis pipelines. A.V.V. and A.P. assisted in other statistical analyses, interpretation of data, and drafting of the manuscript. R.M.D., M.F.E., A.W.G.-N., D.K., V.C., M.A.Y.K., A.K., A.P., T.J.K., B.H.J., S.P.B., J.S.F.S., M.R.H.-F., R.J.P., F.J.C.C., V.E.d.M., C.W., E.A.M.F., A.Z., J.F., H.J.M.H., H.B., S.J.L.B., and R.K.W. collected data, assisted in study planning, and critically reviewed the manuscript. H.J.M.H., H.B., S.J.L.B., and R.K.W. conceived, coordinated, and supported the study.
Competing interests: R.K.W. acted as consultant for Takeda Pharmaceutical. The other authors declare that they have no competing interests.
Data and materials availability: All data associated with this study are present in the paper or the Supplementary Materials. The raw microbiome sequencing data and basic phenotypes used in this study are available at the European Genome-Phenome Archive under accession numbers EGAD00001008907 (https://ega-archive.org/datasets/EGAD00001008907), EGAS00001006257 (https://ega-archive.org/studies/EGAS00001006257), and EGAS00001006258 (https://ega-archive.org/studies/EGAS00001006258). Access requests to the EGA will be assessed by the UMCG TransplantLines Investigators data access committee and will be granted to all reasonable requests. Scripts used for data analysis can be found at (46) and at https://github.com/GRONINGEN-MICROBIOME-CENTRE/TransplantLines.
Supplementary Materials
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- Beenmergtransplantaties: EPA (eicosapentaenoic acid) vermindert ingeval van beenmergtransplantaties de kans op ernstige complicaties en verlaagt significant de sterfte. Geen tegenover 5 patiënten overleden in groepen van resp. 7 (EPA) en 9 patienten
- Hematopoietische stamceltransplantatie (HCT) blijkt bijzonder effectieve behandeling tegen ziekte van Crohn, waar andere behandelingen door resistentie niet meer mogelijk waren.
- Stamceltransplantaties: De resultaten van allogene stamceltransplantatie zijn afgelopen jaren sterk verbeterd. Algehele overleving stijgt hoogsignificant met 41% en het risico op ernstige graft versus host complicaties verminderde met 67%
- Stamcellen zouden primaire kanker kunnen bestrijden
- Stamceltransplantatie (allogeen) bij recidief van non-Hodgkin geeft 43 procent ziektevrije vijfjaars overleving en 48 procent overall 5 jaars overleving blijkt uit fase II studie met 44 patienten met recidief van non-Hodgkin
- Stamcellen: recente ontwikkelingen
- Beenmergtransplantaties en stamceltransplantaties: Studiepublicaties van niet-toxische middelen en behandelingen uit literatuurlijst van arts-bioloog drs. Engelbert Valstar naast beenmergtransplantaties en stamceltransplantaties
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