Decoding the Interactive Effects of Litchi Pectin and EGCG on Immune Microenvironment Remodeling: A Microbiota–Metabolic–Immune Perspective

Plant-derived pectic polysaccharides and epigallocatechin gallate (EGCG) extensively interact during processing and consumption. Both compounds are known to regulate host immunity, yet their respective roles and combined effects in the microbiota-metabolic-immune axis remain unclear. This study investigated the effects of litchi-derived pectic polysaccharides (SCLP) and EGCG in cyclophosphamide-induced immunocompromised and intestinal barrier-damaged mice. EGCG notably enhanced peripheral immunity by increasing spleen indices, promoting of splenic B cell proliferation, and upregulation of IL-10, IL-6, and TNF-α expression in the spleen. In contrast, SCLP demonstrated superior efficacy in intestinal immune regulation by upregulating the expression of goblet cell, Muc-2, tight junction proteins, and balancing mucosal cytokine secretion. Microbiota analysis revealed SCLP enriched SCFA-producing genera (Bacteroides, Muribaculaceae, Lachnospiraceae_NK4A136_group, Oscillospiraceae) and reduced inflammation-associated phyla (Proteobacteria, Desulfobacterota), while EGCG selectively promoted Akkermansia. Metabolomic profiling showed EGCG activated lipid metabolism and pantothenate-CoA biosynthesis, whereas SCLP enhanced fecal SCFA production, upregulated GPCR43/41 expression, and activated energy-producing pathways including pyruvate metabolism and the TCA cycle. Notably, coadministration did not exhibit synergistic effect on intestinal immune modulation. These findings provide new insight into the distinct and interactive roles of SCLP and EGCG in regulating the gut-immune microenvironment, supporting their application as dietary components for managing immunosuppressive disorders.