Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial

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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 (<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.

Related collections

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Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776). Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): Gut

Journal ID (iso-abbrev): Gut

Journal ID (hwp): gutjnl

Journal ID (publisher-id): gut

Title: Gut

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Print): 0017-5749

ISSN (Electronic): 1468-3288

Publication date (Print): January 2021

Publication date (Electronic): 26 October 2020

Volume: 70

Issue: 1

Pages: 92-105

Affiliations

[1 ] departmentDepartment of Vascular Medicine , Amsterdam University Medical Centres , Amsterdam, Noord-Holland, The Netherlands

[2 ] departmentDepartment of Internal Medicine , LUMC , Leiden, Zuid-Holland, The Netherlands

[3 ] departmentDiabetes Research Institute , IRCCS San Raffaele Scientific Institute , Milan, Italy

[4 ] departmentDiabetes Research Institute , San Raffaele Scientific Institute , Milan, Italy

[5 ] departmentInternal Medicine , OLVG Location West , Amsterdam, North Holland, The Netherlands

[6 ] departmentInternal Medicine , Rijnstate , Arnhem, Gelderland, The Netherlands

[7 ] departmentInternal Medicine , OLVG, Location Oost , Amsterdam, Noord-Holland, The Netherlands

[8 ] departmentInternal Medicine , North West Hospital Group , Alkmaar, Noord-Holland, The Netherlands

[9 ] departmentInternal Medicine , Groene Hart Hospital , Gouda, Zuid-Holland, The Netherlands

[10 ] departmentInternal Medicine , Deventer Hospital , Deventer, Overijssel, The Netherlands

[11 ] departmentInternal Medicine , Hospital Amstelland , Amstelveen, North Holland, The Netherlands

[12 ] departmentDepartment of Epidemiology and Biostatistics , Amsterdam University Medical Centres , Amsterdam, Noord-Holland, The Netherlands

[13 ] departmentDepartment of Gastroenterology , Academic Medical Center , Amsterdam, The Netherlands

[14 ] departmentMicrobiology , WUR , Wageningen, The Netherlands

[15 ] Department of Diabetes Immunology, Diabetes & Metabolism Research Institute at the Beckman Research Institute, City of Hope , Duarte, CA, USA

Author notes

[Correspondence to ] Professor Max Nieuwdorp, Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, Noord-Holland, Netherlands; m.nieuwdorp@ 123456amsterdamumc.nl

Author information

Jacques Bergman http://orcid.org/0000-0001-7548-6955

Lorenzo Piemonti http://orcid.org/0000-0002-2172-2198

Max Nieuwdorp http://orcid.org/0000-0002-1926-7659

Article

Publisher ID: gutjnl-2020-322630

DOI: 10.1136/gutjnl-2020-322630

PMC ID: 7788262

PubMed ID: 33106354

SO-VID: 59de3ca8-3a25-4b6c-a466-7c927d7b63db

License:

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.