Evidence map›Paper›PMID 29653584›Full record

ArticleGenome medicine2018

Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development.

Wei-Hung Pan, Felix Sommer, Maren Falk-Paulsen, Thomas Ulas, Lena Best, Antonella Fazio, Priyadarshini Kachroo, Anne Luzius, Marlene Jentzsch, Ateequr Rehman and 10 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 3 pooled it
6.8field-weighted citation impact, top 2% 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

97 citing papers in PubMed, 3 syntheses or guidelines pooled it, 152 citations in OpenAlex.

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  19. The Gut and Skin Microbiome and Its Association with Aging Clocks.International journal of molecular sciences · 2024
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37 more citing papers are in PubMed but not listed here.

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

20 authors at 7 institutions in 3 countries.

Wei-Hung PanInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Felix SommerInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Maren Falk-PaulsenInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Thomas UlasGenomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115, Bonn, Germany.
Lena BestInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Antonella FazioInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Priyadarshini KachrooInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Anne LuziusInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Marlene JentzschInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Ateequr RehmanInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Fabian MüllerMax Planck Institute for Informatics, 66123, Saarbrücken, Germany.
Thomas LengauerMax Planck Institute for Informatics, 66123, Saarbrücken, Germany.
Jörn WalterDepartment of Genetics, University of Saarland, 66123, Saarbrücken, Germany.
Sven KünzelInstitute for Experimental Medicine, Christian Albrechts University of Kiel, Kiel, Germany.
John F BainesInstitute for Experimental Medicine, Christian Albrechts University of Kiel, Kiel, Germany.
Stefan SchreiberInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Andre FrankeInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Joachim L SchultzeGenomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115, Bonn, Germany.
Fredrik BäckhedThe Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345, Gothenburg, Sweden.
Philip RosenstielInstitute for Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany. p.rosenstiel@mucosa.de.
Kiel University · DESaarland University · DEEpigenomics (Germany) · DEMax Planck Institute for Informatics · DEUniversity Hospital Schleswig-Holstein · DEUniversity of Bonn · DEUniversity of Copenhagen · DK

Funding

European Research Council 615362
6 · The paper itself

Abstract

backgroundThe interplay of epigenetic processes and the intestinal microbiota may play an important role in intestinal development and homeostasis. Previous studies have established that the microbiota regulates a large proportion of the intestinal epithelial transcriptome in the adult host, but microbial effects on DNA methylation and gene expression during early postnatal development are still poorly understood. Here, we sought to investigate the microbial effects on DNA methylation and the transcriptome of intestinal epithelial cells (IECs) during postnatal development.

methodsWe collected IECs from the small intestine of each of five 1-, 4- and 12 to 16-week-old mice representing the infant, juvenile, and adult states, raised either in the presence or absence of a microbiota. The DNA methylation profile was determined using reduced representation bisulfite sequencing (RRBS) and the epithelial transcriptome by RNA sequencing using paired samples from each individual mouse to analyze the link between microbiota, gene expression, and DNA methylation.

resultsWe found that microbiota-dependent and -independent processes act together to shape the postnatal development of the transcriptome and DNA methylation signatures of IECs. The bacterial effect on the transcriptome increased over time, whereas most microbiota-dependent DNA methylation differences were detected already early after birth. Microbiota-responsive transcripts could be attributed to stage-specific cellular programs during postnatal development and regulated gene sets involved primarily immune pathways and metabolic processes. Integrated analysis of the methylome and transcriptome data identified 126 genomic loci at which coupled differential DNA methylation and RNA transcription were associated with the presence of intestinal microbiota. We validated a subset of differentially expressed and methylated genes in an independent mouse cohort, indicating the existence of microbiota-dependent "functional" methylation sites which may impact on long-term gene expression signatures in IECs.

conclusionsOur study represents the first genome-wide analysis of microbiota-mediated effects on maturation of DNA methylation signatures and the transcriptional program of IECs after birth. It indicates that the gut microbiota dynamically modulates large portions of the epithelial transcriptome during postnatal development, but targets only a subset of microbially responsive genes through their DNA methylation status.

Indexed as

Gene Expression Regulation, DevelopmentalAnimalsDNA MethylationEpithelial CellsFemaleGastrointestinal MicrobiomeGenetic LociGrowth and DevelopmentIntestinesMice, Inbred C57BLRNATranscription, GeneticTranscriptomeRNAEpigeneticsIntestinal epithelial cellMethylationMicrobiotaTranscriptomics

Identifiers

PMID29653584
PMCPMC5899322
OpenAlexW2802827720

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Registered trials

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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.