n-3 Polyunsaturated Fatty Acids Improve DSS-Induced Acute Colitis in Mice via Intestinal Barrier Fortification and...

Area of Science:

• Gastroenterology
• Immunology
• Microbiome Research

Background:

• Ulcerative colitis (UC) presents a growing global health challenge, with increasing incidence worldwide.
• n-3 polyunsaturated fatty acids (PUFAs), specifically eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA), are known for their anti-inflammatory properties.
• The precise mechanisms by which EPA and DHA aid intestinal barrier repair in UC require further elucidation.

Purpose of the Study:

• To investigate the therapeutic effects of EPA and DHA, alone and in combination, on acute ulcerative colitis (UC) in a mouse model.
• To elucidate the impact of EPA and DHA on the colonic mucus and mechanical barriers.
• To explore the influence of EPA and DHA on key molecular signaling pathways and gut microbiome composition in UC.

Main Methods:

• Acute UC was induced using dextran sulfate sodium (DSS).
• Therapeutic effects of mesalazine, EPA, DHA, and EPA+DHA were assessed.
• Mucus barrier integrity, mechanical barrier proteins (Claudin-1/Occludin), signaling pathways (PI3K/Akt, TNF-α/NF-κB, GPR120/PKA/CREB), and gut microbiome composition (16S rRNA sequencing) were analyzed.

Main Results:

• Combined EPA+DHA treatment showed optimal efficacy in alleviating colitis by creating an anti-inflammatory colonic lipid microenvironment.
• This intervention improved the mucosal and mechanical barriers by modulating signaling pathways (PI3K/Akt/NHE3, TNF-α/NF-κB/DRA, GPR120/PKA/CREB/AQP).
• EPA+DHA significantly enhanced beneficial gut bacteria, including Lachnospiraceae and Ruminococcaceae.

Conclusions:

• Combined EPA+DHA effectively alleviates acute UC in mice.
• This therapeutic strategy fortifies the colonic mucus-mechanical dual barrier and regulates gut microbiome homeostasis.
• EPA+DHA represents a potential novel adjunctive treatment for UC.