REGγ Mitigates Radiation-Induced Enteritis by Preserving Mucin Secretion and Sustaining Microbiome Homeostasis

Area of Science:

• Gastroenterology
• Microbiology
• Radiation Oncology

Background:

• Radiation-induced enteritis is a common side effect of abdominal radiation therapy, often linked to gut microbiota dysbiosis.
• The intestinal mucus layer is critical for preventing microbial translocation and maintaining gut homeostasis.
• The role of REGγ (also known as NME7) in intestinal health, particularly its influence on the mucus layer and gut microbiota, is not well understood.

Purpose of the Study:

• To investigate the role of REGγ in the intestinal response to radiation.
• To determine if REGγ influences gut microbiota composition and mucus layer integrity after irradiation.
• To elucidate the mechanisms by which REGγ may protect against radiation-induced enteritis.

Main Methods:

• Irradiated REGγ knockout and wild-type mice were used to assess gut microbiota, metabolites, and inflammatory responses.
• Fluorescence in situ hybridization was employed to visualize bacterial proximity to intestinal epithelial cells.
• Goblet cell populations and expression of goblet cell markers (Muc2, Tff3) were analyzed in murine models, organoids, and human cells.
• The effect of broad-spectrum antibiotics on inflammation in REGγ-deficient mice was evaluated.

Main Results:

• REGγ deficiency led to significant gut microbiota and metabolite alterations in irradiated mice.
• Absence of REGγ exacerbated intestinal inflammation, characterized by increased neutrophil and macrophage infiltration.
• REGγ knockout mice showed increased bacterial proximity to the intestinal epithelium post-irradiation.
• REGγ deficiency resulted in reduced goblet cell numbers and decreased expression of Muc2 and Tff3.
• Antibiotic treatment attenuated ileal inflammation in irradiated REGγ-deficient mice, suggesting a role for microbial imbalance.

Conclusions:

• REGγ plays a critical role in maintaining gut barrier function and regulating mucus secretion in response to radiation.
• REGγ deficiency contributes to radiation-induced enteritis by promoting gut dysbiosis and compromising the mucus layer.
• Targeting REGγ or managing gut microbiota may offer therapeutic strategies for mitigating radiation enteritis.