Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial
Authors: Daniel van Raalte
Frank Stam
Max Nieuwdorp
Catherina Brouwer
Pieter de Groot
Tanja Nikolic
Gaby Duinkerken
Han Levels
Martin Gerding
Bernadette de Bakker
Joost Hoekstra
Ilias Attaye
Valeria Sordi
Elena Rampanelli
Lorenzo Piemonti
Martin Diekman
Antoinette Joosten
Suat Simsek
Guido Bakker
Sultan Imangaliyev
Evgeni Levin
Sytze van Dam
Bartjan Potter van Loon
Aeilko Zwinderman
Victor Gerdes
Bart Roep
Nordin Hanssen
Frits Holleman
Andrei Prodan
Arianne van Bon
Cees Rustemeijer
Jacques Bergman
Willem De Vos
Roel Hoogma
Silvia Pellegrini
Journal: Gut (2021)
Discipline: CLINICAL MEDICINE
Keywords: diabetes mellitus.
Affiliations: Department of Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, Noord-Holland, The Netherlands., Department of Internal Medicine, LUMC, Leiden, Zuid-Holland, The Netherlands., Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy., Internal Medicine, OLVG Location West, Amsterdam, North Holland, The Netherlands., Internal Medicine, Rijnstate, Arnhem, Gelderland, The Netherlands., Internal Medicine, OLVG, Location Oost, Amsterdam, Noord-Holland, The Netherlands., Internal Medicine, North West Hospital Group, Alkmaar, Noord-Holland, The Netherlands., Internal Medicine, Groene Hart Hospital, Gouda, Zuid-Holland, The Netherlands., Internal Medicine, Deventer Hospital, Deventer, Overijssel, The Netherlands., Internal Medicine, Hospital Amstelland, Amstelveen, North Holland, The Netherlands., Department of Epidemiology and Biostatistics, Amsterdam University Medical Centres, Amsterdam, Noord-Holland, The Netherlands., Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands., Microbiology, WUR, Wageningen, The Netherlands., Department of Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, Noord-Holland, The Netherlands .

Abstract:  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 (&lt;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. 

Retracted: No

PubPeer comments:
 **Retracted** on 22 November 2021: https: link.springer.com article 10.1007 s12517-021-09047-2  The Editor-in-Chief and the Publisher have retracted this article because the content of this article is nonsensical. The peer review process was not carried out in accordance with the Publisher s peer review policy. The authors have not responded to correspondence regarding this retraction. Retraction followed after earlier Editorial Expression of Concern: https: link.springer.com article 10.1007 s12517-021-08470-9  Following the publication of this topical collection of the Arabian Journal of Geosciences, the Publisher became aware of serious research integrity concerns within the collection. The peer review process was not carried out in accordance with the Publisheru2019s peer review policy (see https: www.springer.com gp editorial-policies peer-review-policy-process), and may have been deliberately manipulated. All articles in this topical collection are currently being assessed. The Publisher will take further editorial action where appropriate, once this investigation is complete. The authors were informed of the publication of this Editorial Expression of Concern using email addresses provided at submission. This topic has been covered by Retraction Watch: https: retractionwatch.com 2021 09 28 springer-nature-slaps-more-than-400-papers-with-expressions-of-concern-all-at-once ,