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

BACKGROUND

The increasing global burden of ulcerative colitis (UC) is showing a high incidence in developed countries and a swift rise in developing countries. n-3 polyunsaturated fatty acids (PUFAs), particularly eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA), have demonstrated anti-inflammatory effects. However, their exact mechanisms in intestinal barrier repair for UC remain incompletely elucidated.

METHODS

Acute UC was induced using 2% dextran sulfate sodium (DSS) and the therapeutic effects of mesalazine, EPA, DHA, and EPA + DHA were evaluated. The mucus barrier was assessed histologically. RT-qPCR and Western blot were used to quantify the expression of Mucin2, mechanical barrier proteins (Claudin-1/Occludin), and key signaling pathways (PI3K/Akt, TNF-α/NF-κB, GPR120/PKA/CREB). Gut microbiome composition was analyzed via 16S rRNA sequencing.

RESULTS

EPA + DHA intervention demonstrated optimal efficacy in alleviating colitis, through establishing an anti-inflammatory colonic lipid microenvironment by elevating the EPA/AA and DHA/AA ratios. Inhibiting PI3K/Akt/NHE3, downregulating TNF-α/NF-κB/DRA, activating GPR120/PKA/CREB/AQP) improved the mucosal barrier and restored tight junction to enhance the mechanical barrier. Furthermore, EPA + DHA significantly increased the abundance of beneficial microbiome like Lachnospiraceae and Ruminococcaceae.

CONCLUSION

EPA + DHA effectively alleviates acute UC in mice by fortifying the colonic mucus-mechanical dual barrier and regulating gut microbiome homeostasis, providing a novel potential strategy for UC adjunctive treatment.