Myo-inositol reduces β-catenin activation in colitis

Area of Science:

• Gastroenterology and Hepatology
• Oncology
• Stem Cell Biology

Background:

• Inflammation in colitis can lead to dysplasia and cancer.
• Identifying reliable biomarkers for dysplasia is crucial for effective chemoprevention.
• Dietary interventions are being explored for their therapeutic potential in inflammatory bowel diseases.

Purpose of the Study:

• To investigate the efficacy of dietary myo-inositol in mitigating intestinal stem cell activation during colitis.
• To validate phospho-beta-catenin at serine 552 (pβ-catenin^S552) as a biomarker for recurrent dysplasia.
• To assess the role of pβ-catenin^S552 in colitis-associated dysplasia and cancer.

Main Methods:

• Utilized IL-10 knockout and dextran sodium sulfate-induced colitis mouse models.
• Assessed inflammation, pβ-catenin^S552, and pAkt levels via histology and western blot.
• Conducted a pilot clinical trial with myo-inositol in patients with a history of low-grade dysplasia (LGD) and analyzed pβ-catenin^S552 in human subjects.

Main Results:

• Dietary myo-inositol treatment reduced inflammation and intestinal stem cell activation in mice, as indicated by pβ-catenin^S552 staining.
• In a pilot clinical trial, patients receiving myo-inositol showed reduced stem cell activation compared to placebo.
• pβ-catenin^S552 staining effectively differentiated ulcerative colitis patients with a history of LGD from those with benign disease.

Conclusions:

• Dietary myo-inositol demonstrates potential in reducing stem cell activation in colitis.
• pβ-catenin^S552 is a validated biomarker for recurrent dysplasia in colitis.
• Quantifying crypts with increased pβ-catenin^S552-positive cells can aid in colitis-associated cancer chemoprevention trials.