Pieter de Groot, Tanja Nikolic, Silvia Pellegrini, Valeria Sordi, Sultan Imangaliyev, Elena Rampanelli, Nordin Hanssen, Ilias Attaye, Guido Bakker, Gaby Duinkerken, Antoinette Joosten, Andrei Prodan, Evgeni Levin, Han Levels, Bartjan Potter van Loon, Arianne van Bon, Catherina Brouwer, Sytze van Dam, Suat Simsek, Daniel van Raalte, Frank Stam, Victor Gerdes, Roel Hoogma, Martin Diekman, Martin Gerding, Cees Rustemeijer, Bernadette de Bakker, Joost Hoekstra, Aeilko Zwinderman, Jacques Bergman, Frits Holleman, Lorenzo Piemonti, Willem De Vos, Bart Roep, Max Nieuwdorp
Objective Type 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).
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.