Evidence map›Paper›PMID 41707315›Full record

ArticleNeoplasia (New York, N.Y.)2026

Microbe-associated molecular patterns differentially mediate carcinogenic alterations of the breast tissue in the context of obesity.

Mohamed Gaber, Lauren M Moulden, Adam S Wilson, Valerie Payne, Julia Holmes, Kayla Neary, Abigail Peoples, Mary L Duet, Adam J Katz, Pierre-Alexandre Vidi and 1 more

Abstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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

3 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
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

11 authors.

Mohamed GaberDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
Lauren M MouldenDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
Adam S WilsonDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
Valerie PayneDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
Julia HolmesDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
Kayla NearyDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
Abigail PeoplesDepartment of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Mary L DuetDepartment of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Adam J KatzDepartment of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Pierre-Alexandre VidiInstitut de Cancérologie de l'Ouest, Angers, 49055, France. Electronic address: pierre.vidi@ico.unicancer.fr.
Katherine L CookDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA; Department of Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA; Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA. Electronic address: klcook@wakehealth.edu.

Funding

Tumor Tissue CoreP30CA012197 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Ruben A. Mesa · 1985 to 2026
$55.4M
Institut National du CancerNCI NIH HHS P30 CA012197
6 · The paper itself

Abstract

Obesity is a risk factor for breast cancer. Obesity alters the microbiome and microbiome perturbations are reported in breast cancer patients. Yet, the impact of obesity-mediated microbial shifts on breast cancer risk remains unclear. Here, we investigate the effect of microbial-associated molecular pattern (MAMP) signaling on genome instability and inflammation. We show in human samples that obesity chronically elevates breast tissue levels of two MAMPs: lipopolysaccharide (LPS) and flagellin. In contrast, obesity was not associated with chronic elevations in lipoteichoic acid (LTA). Injections of LPS and flagellin in mouse mammary glands (MG) were sufficient to induce DNA damage and inflammation. Moreover, DNA damage was reduced in MG of animals on a high-fat diet by knockdown of toll-like receptors for LPS and flagellin (TLR4 and TLR5), but not TLR2 (LTA receptor). Experiments with breast acini cultures demonstrated LPS and flagellin (but not LTA) induce DNA double-strand breaks via TLR and reactive oxygen species (ROS) generation. Similarly, LPS and flagellin mediated nuclear factor-kappa B (NF-κB) pathway activation and increased expression of inflammatory cytokines. Analyses of non-cancerous breast tissue microbiome revealed an enrichment of Proteobacteria in obese women. Proteobacteria often contain LPS and many of these bacteria are flagellated. Tissue-resident Proteobacteria abundance correlated with breast tissue DNA damage. Our findings show that LPS and flagellin are systemic and local mediators of obesity-induced microbiome alterations, predisposing the breast to pre-malignant changes. These results underscore the importance of considering the tissue-resident microbiome as a biomarker of risk to improve primary prevention of breast cancer. Significance: Obesity differentially modulates non-cancerous breast tissue microbial-associated molecular pattern signaling, enriching LPS and flagellin, to promote oxidative stress and DNA damage.

Indexed as

Breast NeoplasmsMicrobiotaObesityAnimalsDNA DamageFemaleFlagellinHumansInflammationLipopolysaccharidesMiceReactive Oxygen SpeciesSignal TransductionTeichoic AcidsToll-Like ReceptorsFlagellinLipopolysaccharidesReactive Oxygen SpeciesTeichoic AcidsToll-Like ReceptorsBreast CancerDNA damageFlagellinInflammationLipopolysaccharideLipoteichoic AcidMicrobiomeObesityPreventionProteobacteriaReactive Oxygen Species (ROS)

Identifiers

PMID41707315
PMCPMC12925586

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.