Evidence map›Paper›PMID 34389700›Full record

ArticleNutrition & diabetes2021

Metformin alleviates choline diet-induced TMAO elevation in C57BL/6J mice by influencing gut-microbiota composition and functionality.

Chunyan Su, Xingxing Li, Yuxin Yang, Yu Du, Xiumin Zhang, Li Wang, Bin Hong

Open access · goldFull text read
In one paragraph

Article in Nutrition & diabetes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 25% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Trimethylamine-Annals of medicine · 2025
    Review
  5. Review
  6. Review
  7. Review
  8. The microbial metabolite trimethylamine N-oxide and the kidney diseases.Frontiers in cellular and infection microbiology · 2025
    Review
  9. Metformin: Past, Present, and Future.Current diabetes reports · 2024
    Review
  10. Review
  11. Review
  12. Review
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

7 authors at 1 institution in 1 country.

Chunyan Su *NHC Key Laboratory of Biotechnology of Antibiotics, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Tiantan Xili, Beijing, 100050, China.
Xingxing Li *NHC Key Laboratory of Biotechnology of Antibiotics, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Tiantan Xili, Beijing, 100050, China.
Yuxin YangNHC Key Laboratory of Biotechnology of Antibiotics, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Tiantan Xili, Beijing, 100050, China.
Yu DuNHC Key Laboratory of Biotechnology of Antibiotics, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Tiantan Xili, Beijing, 100050, China.ORCID 0000-0002-4901-6746
Xiumin ZhangNHC Key Laboratory of Biotechnology of Antibiotics, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Tiantan Xili, Beijing, 100050, China.
Li WangNHC Key Laboratory of Biotechnology of Antibiotics, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Tiantan Xili, Beijing, 100050, China. wangli_imb@163.com.
Bin HongNHC Key Laboratory of Biotechnology of Antibiotics, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Tiantan Xili, Beijing, 100050, China. binhong69@hotmail.com.ORCID 0000-0001-6244-8298
Chinese Academy of Medical Sciences & Peking Union Medical College · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81473214National Natural Science Foundation of China (National Science Foundation of China) 81621064
6 · The paper itself

Abstract

Trimethylamine-N-oxide (TMAO), a gut-microbiota-dependent metabolite generated from its dietary precursors such as choline, has been identified as an independent risk factor for atherosclerosis. Metformin is the most widely used drug for the treatment of type 2 diabetes (T2D), which has therapeutic effects on hyperglycemia accelerated atherosclerosis. A growing body of evidence suggest that metformin plays a therapeutic role by regulating the structure and metabolic function of gut microbiota. However, whether metformin has an impact on gut-microbiota-mediated TMAO production from choline remains obscure. In this study, the oral administration of metformin significantly reduced choline diet-increased serum TMAO in choline diet-fed C57BL/6J mice. The diversity analysis based on 16S rRNA gene sequencing of C57BL/6J mice fecal samples indicated that metformin markedly changed the gut-microbiota composition. Metformin was positively correlated with the enrichment of different intestinal bacteria such as Bifidobacterium and Akkermansia and a lower cutC (a choline utilization gene) abundance. Furthermore, the ex vivo and in vitro inhibitory effects of metformin on choline metabolism of TMA-producing bacteria were confirmed under anaerobic condition. The results suggested that metformin suppresses serum TMAO level by remodeling gut microbiota involved in TMA generation from choline.

Indexed as

AkkermansiaAnimalsAtherosclerosisBifidobacteriumCholineDiabetes Mellitus, Type 2DietDysbiosisFemaleGastrointestinal MicrobiomeHumansMetforminMethylaminesMiceMice, Inbred C57BLRNA, Ribosomal, 16SCholineMetforminMethylaminesRNA, Ribosomal, 16Strimethyloxamine

Identifiers

PMID34389700
PMCPMC8363624
OpenAlexW3190045315

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Registered trials

None linked

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.