Lychee (Litchi chinensis Sonn.) Pulp Phenolics Activate the Short-Chain Fatty Acid-Free Fatty Acid Receptor Anti-inflammatory Pathway by Regulating Microbiota and Mitigate Intestinal Barrier Damage in Dextran Sulfate Sodium-Induced Colitis in Mice

The preventive effect of lychee pulp phenolics (LPP) on dextran sulfate sodium (DSS)-induced colitis of mice and its underlying mechanisms were investigated in this research. LPP supplementation mitigated DSS-induced breakage of the gut barrier as evidenced by the increased tight junction proteins and the enhanced integrity of epithelial cells. Both LPP and 5-ASA treatments could downregulate the expressions of toll-like receptor 4 (TLR-4), NOD protein-like receptor 3 (NLRP3), and proinflammatory cytokines to normal levels. Notably, treatment with LPP at a dosage of 500 mg/kg/day effectively upregulated FFAR2 and FFAR3 expression and contents of short-chain fatty acids (SCFAs), suggesting the activation of the SCFA-FFAR (free fatty acid receptor) pathway. Consistently, the abundances of probiotic taxa and microbiota (Akkermansia, Lactobacillus, Coprococcus, and Bacteroides uniformis) associated with SCFA synthesis were elevated, whereas harmful bacteria (Enterococcus and Aggregatibacter) were suppressed. These data indicate that LPP ameliorates gut barrier damage, activates the microbiota-SCFA-FFAR signaling cascade, and suppresses the TLR4/NLRP3-NF-κB pathway, and therefore, LPP supplementation could be a promising way to protect the intestinal tract.