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Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis.

Publication ,  Journal Article
Soto-Pantoja, DR; Gaber, M; Arnone, AA; Bronson, SM; Cruz-Diaz, N; Wilson, AS; Clear, KYJ; Ramirez, MU; Kucera, GL; Levine, EA; Lelièvre, SA ...
Published in: Cancer Res
July 15, 2021

Obesity and poor diet often go hand-in-hand, altering metabolic signaling and thereby impacting breast cancer risk and outcomes. We have recently demonstrated that dietary patterns modulate mammary microbiota populations. An important and largely open question is whether the microbiome of the gut and mammary gland mediates the dietary effects on breast cancer. To address this, we performed fecal transplants between mice on control or high-fat diets (HFD) and recorded mammary tumor outcomes in a chemical carcinogenesis model. HFD induced protumorigenic effects, which could be mimicked in animals fed a control diet by transplanting HFD-derived microbiota. Fecal transplants altered both the gut and mammary tumor microbiota populations, suggesting a link between the gut and breast microbiomes. HFD increased serum levels of bacterial lipopolysaccharide (LPS), and control diet-derived fecal transplant reduced LPS bioavailability in HFD-fed animals. In vitro models of the normal breast epithelium showed that LPS disrupts tight junctions (TJ) and compromises epithelial permeability. In mice, HFD or fecal transplant from animals on HFD reduced expression of TJ-associated genes in the gut and mammary gland. Furthermore, infecting breast cancer cells with an HFD-derived microbiome increased proliferation, implicating tumor-associated bacteria in cancer signaling. In a double-blind placebo-controlled clinical trial of patients with breast cancer administered fish oil supplements before primary tumor resection, dietary intervention modulated the microbiota in tumors and normal breast tissue. This study demonstrates a link between the gut and breast that mediates the effect of diet on cancer. SIGNIFICANCE: This study demonstrates that diet shifts the microbiome in the gut and the breast tumor microenvironment to affect tumorigenesis, and oral dietary interventions can modulate the tumor microbiota in patients with breast cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/14/3890/F1.large.jpg.

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

July 15, 2021

Volume

81

Issue

14

Start / End Page

3890 / 3904

Location

United States

Related Subject Headings

  • Signal Transduction
  • Oncology & Carcinogenesis
  • Microbiota
  • Mice
  • Humans
  • Female
  • Diet, High-Fat
  • Carcinogenesis
  • Breast
  • Animals
 

Citation

APA
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MLA
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Soto-Pantoja, D. R., Gaber, M., Arnone, A. A., Bronson, S. M., Cruz-Diaz, N., Wilson, A. S., … Cook, K. L. (2021). Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis. Cancer Res, 81(14), 3890–3904. https://doi.org/10.1158/0008-5472.CAN-20-2983
Soto-Pantoja, David R., Mohamed Gaber, Alana A. Arnone, Steven M. Bronson, Nildris Cruz-Diaz, Adam S. Wilson, Kenysha Y. J. Clear, et al. “Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis.Cancer Res 81, no. 14 (July 15, 2021): 3890–3904. https://doi.org/10.1158/0008-5472.CAN-20-2983.
Soto-Pantoja DR, Gaber M, Arnone AA, Bronson SM, Cruz-Diaz N, Wilson AS, et al. Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis. Cancer Res. 2021 Jul 15;81(14):3890–904.
Soto-Pantoja, David R., et al. “Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis.Cancer Res, vol. 81, no. 14, July 2021, pp. 3890–904. Pubmed, doi:10.1158/0008-5472.CAN-20-2983.
Soto-Pantoja DR, Gaber M, Arnone AA, Bronson SM, Cruz-Diaz N, Wilson AS, Clear KYJ, Ramirez MU, Kucera GL, Levine EA, Lelièvre SA, Chaboub L, Chiba A, Yadav H, Vidi P-A, Cook KL. Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis. Cancer Res. 2021 Jul 15;81(14):3890–3904.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

July 15, 2021

Volume

81

Issue

14

Start / End Page

3890 / 3904

Location

United States

Related Subject Headings

  • Signal Transduction
  • Oncology & Carcinogenesis
  • Microbiota
  • Mice
  • Humans
  • Female
  • Diet, High-Fat
  • Carcinogenesis
  • Breast
  • Animals