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Man Luo1, Yuanyuan Chen1, Xiangyang Pan1

  • 1Reproductive Medicine Center, Hunan Provincial Maternal and Child Health Hospital (Hunan Provincial Reproductive Medicine Institution), Changsha, China.

Frontiers in Immunology
|June 5, 2023
PubMed
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Probiotic Escherichia coli Nissle 1917 (EcN) improves polycystic ovary syndrome (PCOS) by restoring sex hormones, ovarian function, and gut microbiota balance. It also reduces mitochondrial damage in granulosa cells, offering a potential therapeutic avenue for PCOS.

Area of Science:

  • Reproductive Endocrinology
  • Microbiome Research
  • Metabolic Disorders

Background:

  • Polycystic ovary syndrome (PCOS) is linked to gut microbiota dysbiosis, metabolic dysfunction, and ovarian issues.
  • Gut metabolites and microbiota play a role in regulating ovarian dysfunction and insulin resistance in PCOS.
  • Escherichia coli Nissle 1917 (EcN) is a probiotic with a proven safety record for gut and immune disorders.

Purpose of the Study:

  • To investigate the therapeutic potential of probiotic EcN in PCOS.
  • To explore the role of the gut microbiota-metabolism-IL-22-mitochondrial damage axis in PCOS.
  • To evaluate EcN's effects on ovarian function, insulin resistance, and gut microbiome in PCOS models.

Main Methods:

  • PCOS mouse models were induced using dehydroepiandrosterone (DHEA) and treated with EcN, fecal microbiota transplantation (FMT), or IL-22 inhibitors.
Keywords:
E. coli Nissle 1917IL-22microbial metabolismmitochondrial injurypolycystic ovary syndrome

Related Experiment Videos

  • Serum and follicular fluid analyses included sex hormones, insulin, glucose, and inflammatory markers.
  • Ovarian tissue morphology, granulosa cell mitochondrial function (JC-1, COX4), autophagy markers, gut microbiota composition (16S rRNA), and metabolites (LC-MS/MS) were assessed.

    • Main Results:

    • EcN treatment restored sex hormone levels and ovarian morphology, increased IL-22, COX4, and PR-A expression, and inhibited mitophagy in PCOS mice.
    • EcN modulated gut microbiota, increasing beneficial genera like Adlercreutzia and Ileibacterium, and improved amino sugar and nucleotide sugar metabolism.
    • FMT confirmed EcN's mechanism via gut microbiota, while IL-22 inhibition blocked the amelioration of mitochondrial damage; clinical samples showed reduced IL-22 and mitochondrial damage in PCOS patients.

    Conclusions:

    • Probiotic EcN effectively ameliorates PCOS symptoms by improving sex hormone profiles, ovarian morphology, and gut microbiota metabolism.
    • EcN enhances IL-22 levels and mitigates mitochondrial damage in granulosa cells, suggesting a key role in the gut-ovarian axis.
    • These findings highlight EcN as a promising therapeutic agent for PCOS, targeting the gut microbiota-metabolism-IL-22-mitochondrial damage pathway.