Genistein Inhibits Clostridioides difficile Infection via Estrogen Receptors and Lysine-Deficient Protein Kinase 1

Area of Science:

• Microbiology
• Immunology
• Endocrinology

Background:

• Clostridioides difficile infection (CDI) is a significant nosocomial disease.
• Postmenopausal women exhibit increased CDI risk, suggesting a role for estrogen.
• Soy products contain genistein, a prominent estrogenic isoflavone.

Purpose of the Study:

• To investigate the anti-inflammatory and antiapoptotic effects of genistein.
• To evaluate the therapeutic potential of oral genistein in CDI models.

Main Methods:

• Primary human cells and colonic tissues were used to assess genistein's effects.
• Animal models (mice and hamsters) were employed to study oral genistein therapy.
• Key molecular pathways, including estrogen receptor and WNK1 signaling, were investigated.

Main Results:

• Genistein administration increased survival rates in mice with CDI.
• Genistein significantly reduced pro-inflammatory cytokine (MIP-1α) secretion in human cells and tissues.
• Genistein inhibited apoptosis and modulated BAX expression in colonic epithelial cells.

Conclusions:

• Genistein demonstrates potent anti-inflammatory and antiapoptotic properties relevant to CDI.
• The protective effects of genistein are mediated through the estrogen receptor/G-protein coupled estrogen receptor/WNK1 signaling cascade.
• Genistein represents a potential therapeutic agent for managing Clostridioides difficile infection.