Evidence mapPaperPMID 40799516Full record

ReviewFrontiers in nutrition2025

Diabetes-preventive molecular mechanisms of breast versus formula feeding: new insights into the impact of milk on stem cell Wnt signaling.

Bodo C Melnik, Ralf Weiskirchen, Sabine Weiskirchen, Wolfgang Stremmel, Swen M John, Claus Leitzmann, Gerd Schmitz

Abstract readReview
In one paragraph

Review in Frontiers in nutrition, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
field-weighted citation impact
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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. 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.

Bodo C MelnikDepartment of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück, Germany.
Ralf WeiskirchenInstitute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, Aachen, Germany.
Sabine WeiskirchenInstitute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, Aachen, Germany.
Wolfgang StremmelPraxis for Internal Medicine, Baden-Baden, Germany.
Swen M JohnDepartment of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück, Germany.
Claus LeitzmannInstitut für Ernährungswissenschaft, University of Gießen, Gießen, Germany.
Gerd SchmitzInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, Regensburg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human milk serves as a transmitter for epigenetic programming involved in postnatal tissue development and organ maturation of the infant. In contrast to formula feeding (FF), prolonged breastfeeding (BF) has been associated with diabetes-preventive effects. Polymorphisms of the transcription factor 7-like 2 (TCF7L2), the key downstream effector of Wingless (Wnt) signaling, increase the risk of diabetes mellitus. Wnt signaling is crucial for β-cell development and proliferation. However, there is limited information regarding Wnt/β-catenin/TCF7L2-dependent effects of BF versus FF on postnatal β-cell progenitor cell development, β-cell proliferation and β-cell mass expansion. The objective of our literature review is to collect and analyze data to provide translational evidence that different components of human milk promote Wnt signaling. We will specifically focus on the variations in Wnt signaling in enteroendocrine L-cells and pancreatic β-cells in response to either FF or BF. FF-induced overstimulation of mTORC1 may suppress Wnt gene expression through S6K1-mediated histone H3K27 trimethylation (H3K27me3). Moreover, the absence of milk exosomal miRNAs in formula that target mRNAs of crucial Wnt inhibitors, as well as reduced levels of eicosapentaenoic acid and glutamine in formula, may further hinder appropriate Wnt signaling, negatively impacting intestinal stem cells, enteroendocrine L-cells and potentially β-cell progenitor cells. Overall, the evidence presented supports the conclusion that FF has a detrimental impact on the Wnt/β-catenin/TCF7L2-regulated enteroendocrine-islet axis, disrupting proper β-cell maturation and proliferation. We propose that human milk, compared to formula, offers optimized conditions for physiological Wnt signaling promoting adequate neonatal β-cell mass expansion, which could explain the early diabetes-preventive effects of prolonged BF.

Indexed as

breastfeedingdiabetes mellitusdiabetes preventionformula feedingmicroRNAmilk exosomewingless signalingβ-cell

Identifiers

PMID40799516
PMCPMC12341479

What Socratic holds

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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 Socratic graph.