Evidence map›Paper›PMID 30397356›Full record

ArticleNature medicine2018

Gut microbiota and intestinal FXR mediate the clinical benefits of metformin.

Lulu Sun, Cen Xie, Guang Wang, Yue Wu, Qing Wu, Xuemei Wang, Jia Liu, Yangyang Deng, Jialin Xia, Bo Chen and 18 more

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04841668 (Gut-Brain-axis), which is not on this map. Cited by 574 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
574citing papers in PubMed, 4 pooled it
29.4field-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.

NCT04841668 completedstarted 2021, after this paper: background citation

Gut-Brain-axis: Targets for Improvement of Cognition in the Elderly

Ran2021Enrolled50Registered outcomes51Posted comparisons0ConditionsType 2 Diabetes MellitusArmsMetformin
PMID 8013758PMID 16443885PMID 11118008PMID 18220635PMID 12086935PMID 28500216PMID 12930161PMID 16219009PMID 11602624PMID 18347351PMID 10718348PMID 16360788other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

574 citing papers in PubMed, 4 syntheses or guidelines pooled it, 981 citations in OpenAlex.

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514 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 7 institutions in 3 countries.

Lulu SunDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Cen XieLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Guang WangDepartment of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Yue WuDepartment of Cardiology, Key Laboratory of Environment and Genes Related to Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Qing WuDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Xuemei WangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Jia LiuDepartment of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Yangyang DengDepartment of Cardiology, Key Laboratory of Environment and Genes Related to Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.ORCID http://orcid.org/0000-0002-6470-2891
Jialin XiaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Bo ChenDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Songyang ZhangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Chuyu YunDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Guan LianDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Xiujuan ZhangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Heng ZhangDepartment of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
William H BissonDepartment of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA.
Jingmin ShiLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Xiaoxia GaoLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Pupu GeCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Cuihua LiuCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Kristopher W KrauszLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Robert G NicholsDepartment of Molecular Toxicology, The Pennsylvania State University, University Park, PA, USA.
Jingwei CaiDepartment of Molecular Toxicology, The Pennsylvania State University, University Park, PA, USA.
Bipin RimalDepartment of Molecular Toxicology, The Pennsylvania State University, University Park, PA, USA.
Andrew D PattersonDepartment of Molecular Toxicology, The Pennsylvania State University, University Park, PA, USA.ORCID http://orcid.org/0000-0003-2073-0070
Xian WangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Frank J GonzalezLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-7990-2140
Changtao JiangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China. jiangchangtao@bjmu.edu.cn.ORCID http://orcid.org/0000-0002-5206-2372
Peking University · CNNational Institutes of Health · USPennsylvania State University · USCapital Medical University · CNChinese Academy of Sciences · CNFirst Affiliated Hospital of Xi'an Jiaotong University · CNOregon State University · US

Funding

Xenobiotic receptorsZIABC005562 · DIVISION OF BASIC SCIENCES - NCI · 2025 to 2025
$2.6M
TRANSCRIPTIONAL REGULATION OF GENES ENCODING XENOBIOTIC METABOLIZING ENZYMESZ01BC005561 · BASIC SCIENCES · 1996 to 2005
–
Intramural NIH HHS Z01 BC005561NIGMS NIH HHS T32 GM102057NLM NIH HHS T32 LM012415
6 · The paper itself

Abstract

The anti-hyperglycemic effect of metformin is believed to be caused by its direct action on signaling processes in hepatocytes, leading to lower hepatic gluconeogenesis. Recently, metformin was reported to alter the gut microbiota community in humans, suggesting that the hyperglycemia-lowering action of the drug could be the result of modulating the population of gut microbiota. However, the critical microbial signaling metabolites and the host targets associated with the metabolic benefits of metformin remained elusive. Here, we performed metagenomic and metabolomic analysis of samples from individuals with newly diagnosed type 2 diabetes (T2D) naively treated with metformin for 3 d, which revealed that Bacteroides fragilis was decreased and the bile acid glycoursodeoxycholic acid (GUDCA) was increased in the gut. These changes were accompanied by inhibition of intestinal farnesoid X receptor (FXR) signaling. We further found that high-fat-diet (HFD)-fed mice colonized with B. fragilis were predisposed to more severe glucose intolerance, and the metabolic benefits of metformin treatment on glucose intolerance were abrogated. GUDCA was further identified as an intestinal FXR antagonist that improved various metabolic endpoints in mice with established obesity. Thus, we conclude that metformin acts in part through a B. fragilis-GUDCA-intestinal FXR axis to improve metabolic dysfunction, including hyperglycemia.

Indexed as

BacteroidesBile Acids and SaltsDiabetes Mellitus, Type 2Diet, High-FatGastrointestinal MicrobiomeGene Expression Regulation, BacterialGlucose IntoleranceHumansHyperglycemiaMetabolomeMetagenomicsMetforminObesityReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearUrsodeoxycholic AcidBile Acids and Saltsglycoursodeoxycholic acidMetforminReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearUrsodeoxycholic Acid

Identifiers

PMID30397356
PMCPMC6479226
OpenAlexW2898587007

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.