The polysaccharide intervention strategy based on charge-viscosity matching: A study on the targeted mechanism for repairing intestinal barrier damage in mice induced by high-fat diet.

High-fat diet (HFD) disrupts intestinal homeostasis, weakens the integrity of the intestinal barrier and subsequently triggers a series of intestinal health complications such as chronic inflammation. To explore the effect of polysaccharides with different charges and viscosities on the intestinal barrier function of HFD-fed mice, the chitosan, inulin, and soy hull polysaccharide were administered. The colon morphology, intestinal barrier permeability, tight junction protein expression, short chain fatty acid content and intestinal microbiota diversity were assessed through HE/AB-APS staining, in vitro imaging, ELISA, GC-MS, and 16S rDNA gene sequencing. The results showed that the body weight, abdominal fat weight and AFI value of HFD-fed mice were decreased, and the colon length was increased after the three polysaccharides intervention. The levels of blood lipids (LDL-C, T-CHO, and TG) and inflammatory factors (IL-6, IL-1β, TNF-α, and LPS) were also reduced, but the number of goblet cells were improved. The colon morphology, intestinal mucosal integrity and intestinal barrier permeability were restored in HFD-fed mice, and the expression levels of tight junction proteins ZO-1 and Occludin were maintained at normal levels. Notably, chitosan exhibited a more pronounced restorative effect compared to inulin and soy hull polysaccharide. Furthermore, the intervention increased the content of SCFAs (butyric acid, acetic acid, and propionic acid) and the diversity of the intestinal microbiota in HFD-fed mice intestines. The abundance of beneficial bacteria, including Muribaculaceae, Lactobacillus, and Bifidobacterium was improved, while the proliferation of harmful bacteria such as Clostridium was suppressed, thereby the balance of intestinal microbiota was restored.