51. Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial
- Author
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Willem M. de Vos, Lorenzo Piemonti, Andrei Prodan, Nordin M J Hanssen, Frank Stam, Suat Simsek, Bartjan Potter van Loon, Jacques J. Bergman, Evgeni Levin, Victor E. A. Gerdes, Martin Diekman, Catherina Brouwer, Bart O. Roep, Gaby Duinkerken, Sultan Imangaliyev, Valeria Sordi, Antoinette Joosten, Guido J. Bakker, Joost B. L. Hoekstra, Ilias Attaye, Daniël H. van Raalte, Arianne C. van Bon, Martin Gerding, Han Levels, Frits Holleman, Aeilko H. Zwinderman, Cees Rustemeijer, Roel P.L.M. Hoogma, Tanja Nikolic, Elena Rampanelli, Max Nieuwdorp, Bernadette S. de Bakker, Silvia Pellegrini, Pieter F. de Groot, Sytze van Dam, Graduate School, ACS - Diabetes & metabolism, ACS - Amsterdam Cardiovascular Sciences, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Pathology, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Experimental Vascular Medicine, Medical Biology, ARD - Amsterdam Reproduction and Development, Epidemiology and Data Science, APH - Methodology, Gastroenterology and Hepatology, ACS - Heart failure & arrhythmias, Internal medicine, Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and hepatology, Surgery, AGEM - Endocrinology, metabolism and nutrition, de Groot, Pieter, Nicolic, Tanja, Pellegrini, Silvia, Sordi, Valeria, Imangaliyev, Sultan, Rampanelli, Elena, Hanssen, Nordin, Attaye, Ilia, Bakker, Guido, Duinkerken, Gaby, Joosten, Annemarie, Prodan, Andrei, Levin, Evgeni, Levels, Han, Potter van Loon, Bartjan, van Bon, Arianne, Brouwer, Catherina, van Dam, Sytze, Simsek, Suat, van Raalte, Daniel, Stam, Frank, Gerdes, Victor, Hoogma, Roel, Diekman, Martin, Gerding, Martin, Rustemeijer, Cee, de Bakker, Bernadette, Hoekstra, Joost, Zwinderman, Aeilko, Bergman, Jacque, Holleman, Frit, Piemonti, Lorenzo, De Vos, Willem, Roep, Bart, and Nieuwdorp, Max
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Duodenum ,medicine.medical_treatment ,T cell ,030209 endocrinology & metabolism ,medicine.disease_cause ,Gastroenterology ,Transplantation, Autologous ,Microbiology ,Autoimmunity ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Microbiologie ,Internal medicine ,Diabetes mellitus ,Insulin-Secreting Cells ,medicine ,Humans ,Type 1 diabetes ,C-Peptide ,C-peptide ,business.industry ,Insulin ,BacGen ,Fecal Microbiota Transplantation ,medicine.disease ,Pathophysiology ,Gastrointestinal Microbiome ,030104 developmental biology ,medicine.anatomical_structure ,Diabetes Mellitus, Type 1 ,chemistry ,diabetes mellitus ,Female ,Beta cell ,business - Abstract
ObjectiveType 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota–immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT).DesignPatients with recent-onset (ResultsStimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=−0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics.ConclusionFMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D.Trial registration numberNTR3697.
- Published
- 2020
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