Peanut Shell Extract Improves Markers of Glucose Homeostasis in Diabetic Mice by Modulating Gut Dysbiosis and Suppressing Inflammatory Immune Response.

BACKGROUND/OBJECTIVE: There is strong evidence that the tripartite interaction between glucose homeostasis, gut microbiota, and the host immune system plays a critical role in the pathophysiology of type 2 diabetes mellitus (T2DM). We reported previously that peanut shell extract (PSE) improves mitochondrial function in db/db mice by suppressing oxidative stress and inflammation in the liver, brain, and white adipose tissue. This study evaluated the impacts of PSE supplementation on glucose homeostasis, liver histology, intestinal microbiome composition, and the innate immune response in diabetic mice.

METHODS

Fourteen db/db mice were randomly assigned to a diabetic group (DM, AIN-93G diet) and a PSE group (1% wt/wt PSE in the AIN-93G diet) for 5 weeks. Six C57BL/6J mice received the AIN-93G diet for 5 weeks (control group). Parameters of glucose homeostasis included serum insulin, HOMA-IR, HOMA-B, and the analysis of pancreatic tissues for insulin and glucagon. We assessed the innate immune response in the colon and liver using a microarray. Gut microbiome composition of cecal contents was analyzed using 16S rRNA gene amplicon sequencing.

RESULTS

PSE supplementation improved glucose homeostasis (decreased serum insulin concentration, HOMA-IR, and HOMA-B) and reduced hepatic lipidosis in diabetic mice. PSE supplementation reversed DM-induced shifts in the relative abundance of amplicon sequence variants of , , , and . Relative to the DM mice, the PSE group had suppressed gene expression levels of Cd8α, Csf2, and Irf23 and increased expression levels of Tyk2, Myd88, and Gusb in the liver.

CONCLUSIONS

This study demonstrates that PSE supplementation improves T2DM-associated disorders of diabetic mice, in part due to the suppression of innate immune inflammation.