Rhubarb polysaccharides alleviate hypertriglyceridemia-induced acute pancreatitis and regulate gut microbiota-mediated tryptophan metabolism

Rheum tanguticum plays a key role in treating acute pancreatitis, though its bioactive components and mechanisms remain unclear. This study investigates the structural characteristics and therapeutic effects of rhubarb polysaccharides (RP) in a mouse model of hypertriglyceridemia-induced acute pancreatitis (HTGAP). The isolated polysaccharide, (26 kDa, primarily glucose and arabinose) significantly reduced serum amylase and lipase levels, improved pancreatic and intestinal histopathology and upregulated tight junction proteins Zonula Occludens-1 and Occludin. High throughput 16S rRNA sequencing demonstrated that RP supplementation modulated gut microbiota by enriching beneficial genera (e.g., Lactobacillus and Akkermansia ) while reducing pathogenic genera ( Lachnoclostridium , Desulfovibrio ). Untargeted metabolomics revealed alterations in microbial metabolites, particularly in the tryptophan metabolism. Integrated analysis revealed significant microbiota-metabolite correlations. These findings suggest that RP improve HTGAP by restoring intestinal barrier integrity and regulating gut microbiota-mediated tryptophan metabolism, highlighting its potential as a therapeutic agent. • A rhubarb-derived polysaccharide (26 kDa) was characterized, mainly composed of glucose and arabinose. • Polysaccharide treatment reduced serum amylase and LPS levels in HTGAP mouse models. • Expression of tight junction proteins ZO-1 and Occludin increased in intestinal tissue after treatment. • The polysaccharide altered gut microbiota, decreasing Lachnoclostridium, A. indistinctus , and Desulfovibrio. • Metabolomics showed significant changes in tryptophan metabolism related to microbial shifts.