Trial reportDiabetologia2020
Oral butyrate does not affect innate immunity and islet autoimmunity in individuals with longstanding type 1 diabetes: a randomised controlled trial.
Trial report in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 4 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- The Effect of Microbiome-Modulating Agents (MMAs) on Type 1 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Nutrients · 2024Pooled it
- A bibliometric study of global trends in T1DM and intestinal flora research.Frontiers in microbiology · 2024Pooled it
- The Effects of Prebiotics, Synbiotics, and Short-Chain Fatty Acids on Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis.Advances in nutrition (Bethesda, Md.) · 2022Pooled it
- Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes: A systematic review.Frontiers in cellular and infection microbiology · 2022Pooled it
- Effect of curcumin on the gut microbiota of patients with ulcerative colitis, Crohn's disease and healthy participants.Scientific reports · 2026Trial
- Autologous fecal microbiota capsules are safe and potentially preserve beta-cell function in individuals with type 1 diabetes.Gut microbes · 2025Trial
- Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study.Scientific reports · 2022Trial
- Trial
- Translating gut microbiome research into therapies for type 1 diabetes.Experimental physiology · 2026Review
- Mechanisms of Butyrate in Diabetes Through the Metabolism-Immunity Axis and Targeted Therapeutic Strategies.Molecular nutrition & food research · 2026Review
- The HDAC inhibitor sodium butyrate moderately enhances long-term fear extinction memory retrieval in humans.Molecular psychiatry · 2026Article
- Article
- Epigenetic orchestrator and drug enhancer: dual roles of butyrate in regulating post-translational modification and optimizing therapeutic delivery.Cell communication and signaling : CCS · 2025Review
- Unraveling Type 1 Diabetes: Integrating Microbiome, Metabolomics, and Immunomodulation for Next-Generation Therapies.International journal of molecular sciences · 2025Review
- Article
- Gut microbiota-derived short-chain fatty acids and their role in human health and disease.Nature reviews. Microbiology · 2025Review
- Identifying Potential Targets for the Interception of Inflammatory Bowel Disease: Toward Precision Prevention.Inflammatory bowel diseases · 2025Review
- Gut-liver axis in diabetes: Mechanisms and therapeutic opportunities.World journal of gastroenterology · 2025Review
- The role of gut-islet axis in pancreatic islet function and glucose homeostasis.Diabetes, obesity & metabolism · 2025Review
- New Perspectives in Studying Type 1 Diabetes Susceptibility Biomarkers.International journal of molecular sciences · 2025Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 7 institutions in 3 countries.
Funding
Abstract
aims/hypothesisThe pathophysiology of type 1 diabetes has been linked to altered gut microbiota and more specifically to a shortage of intestinal production of the short-chain fatty acid (SCFA) butyrate, which may play key roles in maintaining intestinal epithelial integrity and in human and gut microbial metabolism. Butyrate supplementation can protect against autoimmune diabetes in mouse models. We thus set out to study the effect of oral butyrate vs placebo on glucose regulation and immune variables in human participants with longstanding type 1 diabetes.
methodsWe administered a daily oral dose of 4 g sodium butyrate or placebo for 1 month to 30 individuals with longstanding type 1 diabetes, without comorbidity or medication use, in a randomised (1:1), controlled, double-blind crossover trial, with a washout period of 1 month in between. Participants were randomly allocated to the 'oral sodium butyrate capsules first' or 'oral placebo capsules first' study arm in blocks of five. The clinical investigator received blinded medication from the clinical trial pharmacy. All participants, people doing measurements or examinations, or people assessing the outcomes were blinded to group assignment. The primary outcome was a change in the innate immune phenotype (monocyte subsets and in vitro cytokine production). Secondary outcomes were changes in blood markers of islet autoimmunity (cell counts, lymphocyte stimulation indices and CD8 quantum dot assays), glucose and lipid metabolism, beta cell function (by mixed-meal test), gut microbiota and faecal SCFA. The data was collected at the Amsterdam University Medical Centers.
resultsAll 30 participants were analysed. Faecal butyrate and propionate levels were significantly affected by oral butyrate supplementation and butyrate treatment was safe. However, this modulation of intestinal SCFAs did not result in any significant changes in adaptive or innate immunity, or in any of the other outcome variables. In our discussion, we elaborate on this important discrepancy with previous animal work. CONCLUSIONS/
interpretationOral butyrate supplementation does not significantly affect innate or adaptive immunity in humans with longstanding type 1 diabetes.
trial registrationNetherlands Trial Register: NL4832 (www.trialregister.nl). DATA AVAILABILITY: Raw sequencing data are available in the European Nucleotide Archive repository (https://www.ebi.ac.uk/ena/browse) under study PRJEB30292.
fundingThe study was funded by a Le Ducq consortium grant, a CVON grant, a personal ZONMW-VIDI grant and a Dutch Heart Foundation grant.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.