Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut Microbiota

Area of Science:

• Microbiology
• Pharmacology
• Gastroenterology

Background:

• Ulcerative colitis (UC) involves gut microbiota dysbiosis.
• Marine natural product derivative MR2938 shows promise in alleviating colitis.

Purpose of the Study:

• Investigate MR2938's impact on gut microbiota in dextran sodium sulfate (DSS)-induced colitis.
• Elucidate the role of gut microbiota in MR2938's therapeutic mechanism.

Main Methods:

• Induced colitis in mice using DSS.
• Administered MR2938 (100 mg/kg or 50 mg/kg) and analyzed cecal microbiota via 16S rRNA sequencing.
• Utilized antibiotic-induced microbiome depletion to assess microbiota's role.

Main Results:

• MR2938 modulated gut microbiota composition, altering abundances of key genera like Enterococcus, Staphylococcus, and Lactobacillus.
• Microbiome depletion indicated gut microbiota primarily supports intestinal barrier function.
• MR2938's effect on inflammatory factors was minimal when microbiota was depleted.

Conclusions:

• Intestinal flora play a significant role in the therapeutic effects of MR2938 for colitis.
• MR2938's mechanism involves microbiota-mediated barrier protection.