Cucurbitacin IIb alleviates colitis via regulating gut microbial composition and metabolites

Area of Science:

• Gastroenterology
• Immunology
• Microbiology

Background:

• Cucurbitacin IIb, a triterpenoid, shows promise for intestinal diseases like enteritis.
• Its therapeutic potential for colitis remains unexplored.
• Colitis involves complex inflammatory responses and gut dysbiosis.

Purpose of the Study:

• To investigate the effects and mechanisms of cucurbitacin IIb on dextran sulfate sodium (DSS)-induced colitis in mice.
• To assess its impact on colitis symptoms, inflammation, gut microbiota, and metabolites.

Main Methods:

• Utilized a DSS-induced mouse model of colitis.
• Administered cucurbitacin IIb and evaluated colitis severity, inflammatory markers, and intestinal morphology.
• Analyzed gut microbiota composition and metabolite profiles.
• Conducted antibiotic treatment and fecal microbiota transplantation experiments.

Main Results:

• Cucurbitacin IIb alleviated colitis symptoms, including weight loss and disease activity.
• It reduced inflammatory markers (myeloperoxidase, eosinophil peroxidase), NFκB phosphorylation, and pro-inflammatory cytokines (IL-6, IL-1β).
• Beneficial effects were microbiota-dependent, as evidenced by diminished efficacy with antibiotics and successful transfer via fecal transplantation.

Conclusions:

• Cucurbitacin IIb demonstrates significant anti-inflammatory effects in colitis.
• Its therapeutic action is mediated through the regulation of gut microbiota composition and associated metabolites.
• This study highlights cucurbitacin IIb as a potential therapeutic agent for colitis, acting via gut microbiome modulation.