PPARγ/β/δ Agonists Can Ameliorate Dextran Sodium Sulfate-Induced Colitis and Modulate Gut Microbiota

Area of Science:

• Immunology
• Microbiology
• Pharmacology

Background:

• Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in lipid metabolism and immune responses.
• Dysregulation of PPAR activity is implicated in inflammatory bowel disease (IBD).
• This study investigates the role of PPAR subtypes PPARγ and PPARβ/δ in modulating gut microbiota during IBD.

Purpose of the Study:

• To examine the therapeutic potential of PPARγ and PPARβ/δ agonists in experimental colitis.
• To determine the impact of PPAR modulation on gut microbiota composition and diversity.
• To evaluate the protective effects of PPAR activation against intestinal inflammation.

Main Methods:

• Mice with dextran sulfate sodium (DSS)-induced colitis were treated with PPARγ agonist pioglitazone or PPARβ/δ agonist GW0742, and their respective antagonists.
• Clinical outcomes, colon length, histopathology, and inflammatory markers were assessed.
• Gut microbiota composition was analyzed using 16S rRNA sequencing.

Main Results:

• PPAR agonists pioglitazone and GW0742 significantly ameliorated DSS-induced colitis symptoms and histological damage.
• Antagonists failed to alleviate inflammation and sometimes worsened disease indicators.
• Agonist treatment modulated gut dysbiosis, reducing proinflammatory bacteria and increasing microbial diversity.

Conclusions:

• Activation of PPARγ and PPARβ/δ demonstrates protective effects against experimental colitis.
• Modulating PPAR activity can restore gut microbiota balance in IBD models.
• PPARγ and PPARβ/δ represent promising therapeutic targets for IBD treatment.