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

C-LPE3 relieved colitis symptoms in DSS-induced ulcerative colitis, restoring intestinal barrier integrity.

• The model used was DSS (dextran sulfate sodium)-induced ulcerative colitis (UC) in mice.
• C-LPE3 upregulated tight junction proteins and Muc-2 to restore intestinal barrier integrity.
• The exopolysaccharide was isolated from Lactiplantibacillus plantarum ZGS521.
• Colitis symptoms were alleviated following C-LPE3 treatment.

C-LPE3 suppressed inflammation and oxidative stress by activating AMPK while inhibiting the mTOR/NF-κB cascade.

• The anti-inflammatory mechanism involved activation of AMPK signaling.
• Simultaneously, C-LPE3 inhibited the mTOR/NF-κB signaling cascade.
• Both inflammation and oxidative stress were reduced through this dual pathway modulation.
• In vitro assays confirmed that l-arginine alleviated macrophage inflammation through the same AMPK-mTOR/NF-κB axis.

C-LPE3 reshaped dysbiotic gut microbiota and elevated short-chain fatty acid (SCFA) levels.

• C-LPE3 treatment modulated gut microbiota that had been disrupted (dysbiotic) by DSS-induced colitis.
• Short-chain fatty acid levels were elevated following C-LPE3 treatment.
• Correlation analysis linked C-LPE3-enriched beneficial microbes to higher l-arginine and SCFA levels.
• The microbiota modulation was identified as a key component of the protective mechanism.

C-LPE3 boosted l-arginine biosynthesis by increasing expression of Argininosuccinate Synthase 1 (ASS1) and Argininosuccinate Lyase (ASL).

• Two key enzymes in the arginine biosynthesis pathway were upregulated: ASS1 and ASL.
• Increased l-arginine biosynthesis was identified as a mechanistic link between microbiota modulation and anti-inflammatory effects.
• l-Arginine was shown to alleviate macrophage inflammation through the AMPK-mTOR/NF-κB axis in vitro.
• The overall regulatory mechanism was described as a 'microbiota-l-arginine-AMPK regulatory axis.'

Correlation analysis linked C-LPE3-enriched beneficial microbes to higher l-arginine and SCFA levels, connecting microbiota changes to metabolic outcomes.

• Beneficial microbes enriched by C-LPE3 treatment were positively correlated with l-arginine levels.
• The same beneficial microbes were also correlated with elevated SCFA levels.
• This correlation analysis provided mechanistic support for the microbiota-metabolite-host signaling axis.
• The findings support C-LPE3 development as a gut-health functional food ingredient.