Changes of intestinal microflora of breast cancer in premenopausal women

Eur J Clin Microbiol Infect Dis. 2021 Mar;40(3):503-513. doi: 10.1007/s10096-020-04036-x. Epub 2020 Sep 16.

Abstract

Breast cancer is one of the most common malignant tumors in women. More than half of breast cancer patients are not menopausal at the time of diagnosis. The occurrence and development of premenopausal breast cancer are affected by many factors. Intestinal flora, especially SCFA-producing bacteria, participates in the development of various tumors, and there is a lack of in-depth research in premenopausal breast cancer patients. We used 16S rRNA gene sequencing, targeted metabolomics, and cell culture methods to analyze the changes in the intestinal flora and metabolites of premenopausal breast cancer patients. In addition, we treated breast cancer cells with significantly altered propionate and butyrate in vitro to examine their effects on cell activity. This study followed STROBE guidelines. We found that compared with healthy premenopausal women, the composition and symbiosis of intestinal flora in patients with premenopausal breast cancer changed significantly. The abundance of short-chain fatty acid (SCFA)-producing bacteria was significantly reduced, and the key SCFA-producing enzymes were also significantly reduced. Pediococcus and Desulfovibrio could distinguish premenopausal breast cancer patients from normal premenopausal women. The related propionate and butyrate had a certain ability to inhibit breast cancer cell viability in vitro. As SCFA-producing bacteria, Pediococcus and Desulfovibrio showed potential reference value for the diagnosis of premenopausal breast cancer. The ability of propionate and butyrate to inhibit breast cancer cell lines in vitro suggests that the relevant SCFA receptor may be a new target for the treatment of premenopausal breast cancer.

Keywords: Breast cancer; Intestinal flora; Premenopausal women; Short-chain fatty acid.

MeSH terms

  • Adult
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Bacteria / metabolism
  • Biomarkers, Tumor
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / microbiology*
  • Breast Neoplasms / pathology
  • Butyrates / metabolism
  • Butyrates / pharmacology
  • Cell Survival / drug effects
  • Fatty Acids, Volatile / metabolism
  • Fatty Acids, Volatile / pharmacology
  • Female
  • Gastrointestinal Microbiome* / genetics
  • Humans
  • Premenopause*
  • Propionates / metabolism
  • Propionates / pharmacology
  • RNA, Ribosomal, 16S / genetics
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Butyrates
  • Fatty Acids, Volatile
  • Propionates
  • RNA, Ribosomal, 16S