Evidence map›Paper›PMID 22828956›Full record

ArticleDiabetologia2012

Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice.

B M Carvalho, D Guadagnini, D M L Tsukumo, A A Schenka, P Latuf-Filho, J Vassallo, J C Dias, L T Kubota, J B C Carvalheira, M J A Saad

RetractedOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 147 papers.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed
10.1field-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.

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

147 citing papers in PubMed, 308 citations in OpenAlex.

  1. Trial
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  8. Neuroprotective effects ofFrontiers in nutrition · 2026
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  15. Cancer Cachexia.Advances in experimental medicine and biology · 2025
    Review
  16. Article
  17. Article
  18. Gut bacteria are essential for development of an invasive bark beetle by regulating glucose transport.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  19. Review
  20. Ginsenoside RgNutrients · 2024
    Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

B M CarvalhoInternal Medicine Department-Faculty of Medical Sciences, State University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
D GuadagniniInternal Medicine Department-Faculty of Medical Sciences, State University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
D M L TsukumoInternal Medicine Department-Faculty of Medical Sciences, State University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
A A SchenkaInternal Medicine Department-Faculty of Medical Sciences, State University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
P Latuf-FilhoInternal Medicine Department-Faculty of Medical Sciences, State University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
J VassalloInternal Medicine Department-Faculty of Medical Sciences, State University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
J C DiasChemistry Institute, State University of Campinas, Campinas, São Paulo, Brazil.
L T KubotaChemistry Institute, State University of Campinas, Campinas, São Paulo, Brazil.
J B C CarvalheiraInternal Medicine Department-Faculty of Medical Sciences, State University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
M J A SaadInternal Medicine Department-Faculty of Medical Sciences, State University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil. msaad@fcm.unicamp.br.
Universidade Estadual de Campinas (UNICAMP) · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisA high-fat dietary intake induces obesity and subclinical inflammation, which play important roles in insulin resistance. Recent studies have suggested that increased concentrations of circulating lipopolysaccharide (LPS), promoted by changes in intestinal permeability, may have a pivotal role in insulin resistance. Thus, we investigated the effect of gut microbiota modulation on insulin resistance and macrophage infiltration.

methodsSwiss mice were submitted to a high-fat diet with antibiotics or pair-feeding for 8 weeks. Metagenome analyses were performed on DNA samples from mouse faeces. Blood was collected to determine levels of glucose, insulin, LPS, cytokines and acetate. Liver, muscle and adipose tissue proteins were analysed by western blotting. In addition, liver and adipose tissue were analysed, blinded, using histology and immunohistochemistry.

resultsAntibiotic treatment greatly modified the gut microbiota, reducing levels of Bacteroidetes and Firmicutes, overall bacterial count and circulating LPS levels. This modulation reduced levels of fasting glucose, insulin, TNF-α and IL-6; reduced activation of toll-like receptor 4 (TLR4), c-Jun N-terminal kinase (JNK), inhibitor of κ light polypeptide gene enhancer in B cells, kinase β (IKKβ) and phosphorylated IRS-1 Ser307; and consequently improved glucose tolerance and insulin tolerance and action in metabolically active tissues. In addition, there was an increase in portal levels of circulating acetate, which probably contributed to an increase in 5'-AMP-activated protein kinase (AMPK) phosphorylation in mice. We observed a striking reduction in crown-like structures (CLS) and F4/80(+) macrophage cells in the adipose tissue of antibiotic-treated mice. CONCLUSIONS/

interpretationThese results suggest that modulation of gut microbiota in obesity can improve insulin signalling and glucose tolerance by reducing circulating LPS levels and inflammatory signalling. Modulation also appears to increase levels of circulating acetate, which activates AMPK and finally leads to reduced macrophage infiltration.

Indexed as

AcetatesAMP-Activated Protein Kinase KinasesAnimalsAnti-Bacterial AgentsBacteroidesCell MovementCytokinesDiet, High-FatDisease Models, AnimalGastrointestinal TractInsulinInsulin ResistanceLipopolysaccharidesMacrophagesMaleMetagenomeAcetatesAMP-Activated Protein Kinase KinasesAnti-Bacterial AgentsCytokinesInsulinLipopolysaccharidesProtein Kinases

Identifiers

PMID22828956
OpenAlexW2041255015

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.