An Exopolysaccharide from Lactiplantibacillus plantarum ZGS521 Alleviates Colitis via Gut Microbiota Modulation and Enhanced Arginine Biosynthesis.

This work explored the protective effects and mechanisms of exopolysaccharide C-LPE3 from Lactiplantibacillus plantarum ZGS521 against DSS-induced ulcerative colitis (UC). C-LPE3 relieved colitis symptoms, restored intestinal barrier integrity via upregulating tight junction proteins and Muc-2, and suppressed inflammation and oxidative stress by activating AMPK while inhibiting the mTOR/NF-κB cascade. It reshaped dysbiotic gut microbiota, elevated short-chain fatty acids, and boosted l-arginine biosynthesis by increasing Argininosuccinate Synthase 1 (ASS1)/Argininosuccinate Lyase (ASL) expression. In vitro assays confirmed l-arginine alleviated macrophage inflammation through the AMPK-mTOR/NF-κB axis. Correlation analysis linked C-LPE3-enriched beneficial microbes to higher l-arginine and SCFA levels. Collectively, C-LPE3 mitigates colitis through a microbiota-l-arginine-AMPK regulatory axis, supporting its development as a gut-health functional food ingredient.