Poria cocos triterpenes alleviate diabetes mellitus by regulating the gut microbiota-barrier-inflammation axis and inhibiting the TLR4/nF-κB/NLRP3 pathway.

Diabetes mellitus (DM) is a chronic metabolic disorder characterised by progression associated with dysregulation of gut immunity and impairment of the intestinal barrier. Poria cocos triterpenes (PCT) exhibit hypoglycaemic effects; however, the mechanisms underlying these effects remain inadequately elucidated. We aimed to investigate the anti-diabetic properties of PCT. The findings revealed the identification of 60 PCT components, with 35 being absorbed into the serum of diabetic rats. PCT administration resulted in a significant reduction in blood glucose and lipid levels, restoration of gut microbiota homeostasis, and enhancement of intestinal barrier integrity through the upregulation of ZO-1 and occludin. PCT inhibited the TLR4/NF-κB/NLRP3 pathway and modulated metabolites, such as those involved in tryptophan metabolism, which were correlated with changes in the microbiota. These results suggest that PCT mitigates DM via the gut microbiota-barrier-inflammation axis, underscoring its potential for diabetes management and the integration of medicinal fungi into interventions for metabolic diseases.