Polysaccharide from Aloe vera gel improves intestinal stem cells dysfunction to alleviate intestinal barrier damage via 5-HT.

Metabolites of dietary fibers which consist of non-digestible carbohydrates (usually as plant-based polysaccharides) exert many benefits on gastrointestinal health. Previous studies proved that polysaccharides can change intestinal metabolic pathways, increase metabolite levels and alleviate intestinal inflammation. Our previous studies have shown that polysaccharide from Aloe vera gel (AGP) alleviated intestinal barrier dysfunction. However, whether intestinal protective function of AGP was related to metabolites need further exploration. Therefore, the effects of AGP on intestinal metabolites and the relevant mechanisms for subsequent mitigation of intestinal damage was investigated in this work. Metabolomics analysis results showed that AGP promoted tryptophan metabolism to 5-hydroxytryptamine (5-HT). Intriguingly, antibiotics treatment decreased the expression of tryptophan hydroxylase 1 (TPH1) in the intestinal epithelium of mice, and TPH1 inhibitor (PCPA) down-regulated 5-HT level in colonic contents, proving that AGP up-regulated TPH1 expression in the intestinal epithelium by restoring intestinal microbiota homeostasis, thus promoted the intestinal tryptophan metabolism to 5-HT. Combination of bioinformatics analysis of RNA-sequencing (RNA-Seq) in mice colon and the reported relationship among "5-HT, Htr4 (one of the 5-HT receptors), Kit goblet cells, canonical Wnt pathway and intestinal stem cells (ISCs)" guided the confirmation of related mechanism in intestinal organoids (IOs) that 5-HT regulated ISCs function and intestinal barrier via Htr4-Kit-Wnt3 axis. Overall, AGP promoted 5-HT production to alleviate intestinal injury. This study revealed the effects of polysaccharides on intestinal health, which was critical and may provide new insights for the reasonable selection of dietary fiber to prevent intestinal inflammation and maintain intestinal function.