Dendrobium officinale Polysaccharide Alleviates Type 2 Diabetes Mellitus by Restoring Gut Microbiota and Repairing Intestinal Barrier via the LPS/TLR4/TRIF/NF-kB Axis.

Dendrobium officinale polysaccharide (DOP), the main active component, has a variety of bioactivities. In this study, a type 2 diabetes mellitus (T2DM) and antibiotic-induced pseudo-germ-free mouse models were used to investigate the hypoglycemic mechanisms of DOP. The findings showed that DOP ameliorated dysfunctional glucolipid metabolism, lipopolysaccharide (LPS) leakage, and metabolic inflammation levels in T2DM mice. Furthermore, DOP significantly upregulated the mRNA expression of tight junction proteins Claudin-1 , Occludin , and ZO-1 and reduced intestinal inflammation and oxidative stress damage through the LPS/TLR4/TRIF/NF-κB axis to repair the intestinal barrier. Interestingly, pseudo-germ-free mouse experiments confirmed that the above beneficial effects of DOP were dependent on gut microbiota. 16S rRNA analysis showed that DOP strongly inhibited the harmful bacterium Helicobacter by 94.57% and facilitated the proliferation of probiotics Allobaculum , Bifidobacterium, and Lactobacillus by 34.96, 139.41, and 88.95%, respectively. Therefore, DOP is capable of rebuilding certain specific intestinal microbiota to restore intestinal barrier injury, which supports the utilization of DOP as a new type of prebiotic in functional foods for T2DM.