Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial.
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de Groot Pieter, Nikolic Tanja, Pellegrini Silvia, Sordi Valeria, Imangaliyev Sultan, Rampanelli Elena, Hanssen Nordin, Attaye Ilias, Bakker Guido, Duinkerken Gaby, Joosten Antoinette, 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 Cees, de Bakker Bernadette, Hoekstra Joost, Zwinderman Aeilko, Bergman Jacques, Holleman Frits, Piemonti Lorenzo, De Vos Willem, Roep Bart, Nieuwdorp Max
Аннотация
DESIGN: Patients with recent-onset (<6 weeks) T1D (18-30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition.
RESULTS: Stimulated 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.
CONCLUSION: FMT 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 NUMBER: NTR3697.