Evidence mapPaperPMID 26633628Full record

ArticleNature2015

Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota.

Kristoffer Forslund, Falk Hildebrand, Trine Nielsen, Gwen Falony, Emmanuelle Le Chatelier, Shinichi Sunagawa, Edi Prifti, Sara Vieira-Silva, Valborg Gudmundsdottir, Helle K Pedersen and 20 more

Erratum issued 3 registry-linked trialsOpen access · greenAbstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 3 registered trials, which are not on this map. Cited by 1,115 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,115citing papers in PubMed, 6 pooled it
69.7field-weighted citation impact, top 1% of its field
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.

NCT03031821 phase3terminatedstarted 2018, after this paper: background citation

A Randomized Phase 3 Trial of Metformin in Patients Initiating Androgen Deprivation Therapy as Prevention and Intervention of Metabolic Syndrome: The Prime Study

Ran2018Enrolled166Registered outcomes30Posted comparisons0ConditionsMetabolic Syndrome, Prostate CancerArmsMetformin, Placebo Oral Tablet
Open the trial in the graph
NCT03421301 nacompletednot on this map

A Dietary Intervention With Functional Foods Reduce Metabolic Endotoxemia and Attenuates Biochemical Abnormalities in Subjects With Type 2 Diabetes by Modifying the Gut Microbiota.

TypeinterventionalSponsorInstituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranRan2014 to 2016Enrolled81ConditionsType 2 Diabetes MellitusArmsdietary portfolio
NCT04089280 nacompletednot on this mapstarted 2018, after this paper: background citation

The Effect of Multi-strain Probiotics on Gastrointestinal Symptoms in Patients With Type 2 Diabetes and Metformin Intolerance. A 32-week Prospective, Single Center, Randomized, Placebo Controlled, Cross-over Clinical Trial.

TypeinterventionalSponsorMedical University of SilesiaRan2018 to 2021Enrolled37ConditionsDiabetes Mellitus, Type 2, Metformin Adverse ReactionArmsSanprobi Barrier-multispecies probiotic, Placebo Comparator
3 · Its place in the literature

Who cites it

1,115 citing papers in PubMed, 6 syntheses or guidelines pooled it, 2,068 citations in OpenAlex.

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1,055 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 9 institutions in 9 countries.

Kristoffer Forslund *European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Falk Hildebrand *European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Trine Nielsen *The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Gwen Falony *Center for the Biology of Disease, VIB, Leuven, Belgium.
Emmanuelle Le Chatelier *MICALIS, Institut National de la Recherche Agronomique, Jouy en Josas, France.
Shinichi SunagawaEuropean Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Edi PriftiMICALIS, Institut National de la Recherche Agronomique, Jouy en Josas, France.
Sara Vieira-SilvaCenter for the Biology of Disease, VIB, Leuven, Belgium.
Valborg GudmundsdottirCenter for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
Helle K PedersenCenter for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
Manimozhiyan ArumugamThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Karsten KristiansenDepartment of Biology, University of Copenhagen, Copenhagen, Denmark.
Anita Yvonne VoigtEuropean Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Henrik VestergaardThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Rajna HercogEuropean Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Paul Igor CosteaEuropean Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Jens Roat KultimaEuropean Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Junhua LiBGI-Shenzhen, Shenzhen, China.
Torben JørgensenResearch Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark.
Florence LevenezMICALIS, Institut National de la Recherche Agronomique, Jouy en Josas, France.
Joël DoreMICALIS, Institut National de la Recherche Agronomique, Jouy en Josas, France.
MetaHIT consortium
H Bjørn NielsenCenter for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
Søren BrunakCenter for Biological Sequence Analysis, Dept. of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
Jeroen RaesCenter for the Biology of Disease, VIB, Leuven, Belgium.
Torben HansenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jun WangDepartment of Biology, University of Copenhagen, Copenhagen, Denmark.
S Dusko EhrlichMICALIS, Institut National de la Recherche Agronomique, Jouy en Josas, France.
Peer BorkEuropean Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Oluf PedersenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
University of Copenhagen · DKEuropean Molecular Biology Laboratory · DEMicrobiologie de l’alimentation au service de la santé · FRBGI Group (China) · CNTechnical University of Denmark · DKRega Institute for Medical Research · BEVrije Universiteit Brussel · BEGuy's Hospital · GBHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.

Indexed as

BiodiversityDiabetes Mellitus, Type 2FemaleGastrointestinal MicrobiomeHumansHypoglycemic AgentsMaleMetagenomeMetforminRNA, Ribosomal, 16SHypoglycemic AgentsMetforminRNA, Ribosomal, 16S

Identifiers

PMID26633628
PMCPMC4681099
OpenAlexW2188930066

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

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.