Evidence mapPaperPMID 40665409Full record

Observational studyGenome medicine2025

The dynamics of the gut microbiota in prediabetes during a four-year follow-up among European patients-an IMI-DIRECT prospective study.

Liwei Lyu, Yong Fan, Josef Korbinian Vogt, Marc Clos-Garcia, Amelie Bonnefond, Helle Krogh Pedersen, Avirup Dutta, Robert Koivula, Sapna Sharma, Kristine Højgaard Allin and 45 more

Registry-linked trialAbstract readObservational Study
In one paragraph

Observational study in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03814915 (DIabetes REsearCh on Patient straTification), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT03814915 completednot on this map

DIabetes REsearCh on Patient straTification

TypeobservationalSponsorLund UniversityRan2012 to 2019Enrolled3,049ConditionsType2 Diabetes
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

55 authors.

Liwei Lyu *Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Yong Fan *Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Josef Korbinian Vogt *Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Marc Clos-Garcia *Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Amelie Bonnefond *INSERM UMR 1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille University Hospital, 59000, Lille, France.
Helle Krogh Pedersen *Cmbio (Denmark), Copenhagen, Denmark.
Avirup DuttaNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Robert KoivulaOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
Sapna SharmaInstitute of Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany.
Kristine Højgaard AllinNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Caroline BrorssonSection for Bioinformatics, Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark.
Henna CederbergInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Elizaveta ChabanovaDepartment of Diagnostic Radiology, Copenhagen University Hospital Herlev Gentofte, Herlev, Denmark.
Federico De MasiSection for Bioinformatics, Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark.
Emmanouil DermitzakisDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Petra J EldersDepartment of General Practice, Amsterdam UMC- location VUmc, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Marieke T BlomDepartment of General Practice, Amsterdam UMC- location VUmc, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Monika HollanderDepartment of General Practice, Amsterdam UMC- location VUmc, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Rebeca EriksenSection for Nutrition Research, Faculty of Medicine, Imperial College London, London, UK.
Ian ForgiePopulation Health & Genomics, School of Medicine, University of Dundee, Dundee, UK.
Gary FrostSection for Nutrition Research, Faculty of Medicine, Imperial College London, London, UK.
Giuseppe N GiordanoGenetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University and Helsingborg Hospital, Helsingborg, Sweden.
Harald GrallertGerman Center for Diabetes Research (DZD), Ingolstadter Landstr. 1, Neuherberg, 85764, Germany.
Mark HaidResearch Unit Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
Tue Haldor HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Bernd JablonkaStrategy & Innovation, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.
Tarja KokkolaInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Anubha MahajanWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Andrea MariCNR Institute of Neuroscience, Padova, Italy.
Timothy J McDonaldInstitute of Clinical and Biological Sciences, University of Exeter Medical School, Exeter, UK.
Petra B MusholtR&D Global Development, Translational Medicine & Clinical Pharmacology (TMCP), Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.
Imre PavoEli Lilly , Regional Operations GmbH, Vienna, Austria.
Cornelia PrehnResearch Unit Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany.
Martin RidderstråleClinical Obesity, Department of Clinical Sciences, Lund University Diabetes Centre, CRC, Lund University, Skåne University Hospital, Malmö, Sweden.
Hartmut RuettenBoehringer Ingelheim, International GmbH, Ingelheim am Rhein, Germany.
Leen M 't HartAmsterdam UMC, Location VUmc, Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Jochen M SchwenkAffinity Proteomics, Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of Technology, Solna, Sweden.
Evelina StankevicNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Henrik S ThomsenFaculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Jagadish VangipurapuInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Henrik VestergaardNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Ana ViñuelaPopulation Health & Genomics, School of Medicine, University of Dundee, Dundee, UK.
Mark WalkerTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.
Torben HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Allan LinnebergCenter for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
Henrik Bjørn NielsenCmbio (Denmark), Copenhagen, Denmark.
Søren BrunakSection for Bioinformatics, Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark.
Mark I McCarthyOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
Philippe FroguelOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
Jerzy AdamskiInstitute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg, Germany.
Paul W FranksGenetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University and Helsingborg Hospital, Helsingborg, Sweden.
Marku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Joline W J BeulensAmsterdam UMC, Location VUmc, Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Ewan PearsonPopulation Health & Genomics, School of Medicine, University of Dundee, Dundee, UK.
Oluf PedersenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. oluf@sund.ku.dk.

Funding

European Union's Seventh Framework Programme FP7/2007-2013
6 · The paper itself

Abstract

backgroundPrevious case-control studies have reported aberrations of the gut microbiota in individuals with prediabetes. The primary objective of the present study was to explore the dynamics of the gut microbiota of individuals with prediabetes over 4 years with a secondary aim of relating microbiota dynamics to temporal changes of metabolic phenotypes.

methodsThe study included 486 European patients with prediabetes. Gut microbiota profiling was conducted using shotgun metagenomic sequencing and the same bioinformatics pipelines at study baseline and after 4 years. The same phenotyping protocols and core laboratory analyses were applied at the two timepoints. Phenotyping included anthropometrics and measurement of fasting plasma glucose and insulin levels, mean plasma glucose and insulin under an oral glucose tolerance test (OGTT), 2-h plasma glucose after an OGTT, oral glucose insulin sensitivity index, Matsuda insulin sensitivity index, body mass index, waist circumference, and systolic and diastolic blood pressure. Measures of the dynamics of bacterial microbiota were related to concomitant changes in markers of host metabolism.

resultsOver 4 years, significant declines in richness were observed in gut bacterial and viral species and microbial pathways accompanied by significant changes in the relative abundance and the genetic composition of multiple bacterial species. Additionally, bacterial-viral interactions diminished over time. Despite the overall reduction in bacterial richness and microbial pathway richness, 80 dominant core bacterial species and 78 core microbial pathways were identified at both timepoints in 99% of the individuals, representing a resilient component of the gut microbiota. Over the same period, individuals with prediabetes exhibited a significant increase in glycemia and insulinemia alongside a significant decline in insulin sensitivity. Estimates of the gut bacterial microbiota dynamics were significantly correlated with temporal impairments in host metabolic health.

conclusionsIn this 4-year prospective study of European patients with prediabetes, the gut microbiota exhibited major changes in taxonomic composition, bacterial species genetics, and microbial functional potentials, many of which paralleled an aggravation of host metabolism. Whether the temporal gut microbiota changes represent an adaptation to the progression of metabolic abnormalities or actively contribute to these in prediabetes cases remains unsettled.

trial registrationThe Diabetes Research on Patient Stratification (DIRECT) study, an exploratory observational study initiated on October 15, 2012, was registered on ClinicalTrials.gov under the number NCT03814915.

Indexed as

Gastrointestinal MicrobiomePrediabetic StateAdultAgedBacteriaBlood GlucoseEuropeFemaleFollow-Up StudiesGlucose Tolerance TestHumansMaleMetagenomicsMiddle AgedProspective StudiesBlood GlucoseGut bacterial geneticsGut bacterial microbiotaGut viral microbiotaInsulin sensitivityLong-term dynamicsMetabolismMicrobial functional pathwaysPrediabetes

Identifiers

PMID40665409
PMCPMC12261804

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.