Neohesperidin prevents colorectal tumorigenesis by altering the gut microbiota

Area of Science:

• Biochemistry
• Microbiology
• Oncology

Background:

• Neohesperidin (NHP), a citrus-derived flavonoid, exhibits potential health benefits.
• The role of NHP in cancer prevention, particularly colorectal tumorigenesis, remains largely undetermined.
• Understanding NHP's mechanism against cancer is crucial for therapeutic development.

Purpose of the Study:

• To investigate the effect of Neohesperidin (NHP) on colorectal cancer development.
• To elucidate the underlying mechanisms of NHP's anti-tumorigenic activity.
• To explore the potential role of gut microbiota in NHP's preventative effects.

Main Methods:

• Utilized the APC^min/+ transgenic mouse model for colorectal tumorigenesis studies.
• Performed in-cell assays to assess NHP's direct impact on tumor cells.
• Conducted 16S rRNA gene sequencing to analyze gut microbiota composition changes.
• Implemented fecal microbiota transplantation experiments to validate the role of microbiota.

Main Results:

• NHP significantly inhibited colorectal tumorigenesis in vivo, inducing apoptosis and blocking angiogenesis.
• NHP did not exhibit direct cytotoxic effects on tumor cells in vitro.
• NHP administration altered gut microbiota profiles, decreasing Bacteroidetes and increasing Firmicutes and Proteobacteria.
• Fecal microbiota transplantation from NHP-treated mice conferred protection against tumorigenesis.

Conclusions:

• Neohesperidin (NHP) effectively prevents colorectal tumorigenesis, mediated by alterations in gut microbiota composition.
• The anti-tumorigenic effects of NHP are primarily attributed to its modulation of the gut microbiome.
• NHP represents a promising natural product for colorectal cancer prevention through microbiome manipulation.