Dietary Ginger Root Extract Supplementation Mitigated Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats by Modulating Gut Microbiota

Abstract

ObjectivesDiabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes with no effective treatment currently. The relationship between gut microbiota and neurological diseases, including DNP, has received increasing attention. Previous studies have shown gingerol-enriched gingerol (GEG) has potential pain-reduction and prebiotic abilities due to its anti-inflammatory capacity. This study examined the effect of GEG on pain sensitivity and gut microbiota in DNP rats. MethodsThirty-three male rats were randomly divided into 3 groups: control group (low-fat diet), DPN group (high-fat diet plus single dose of streptozotocin at 36 mg/kg BW), and DPN + GEG at 0.75% in diet for 6 weeks. Von Frey test was used for for pain assessment. 16S rRNA gene sequencing was done from cecal samples and microbiome data analysis was performed using QIIME 2. ResultsRelative to the control group, the DNP group showed increased pain hypersensitivity, measured as decreased mechanical withdrawal thresholds. GEG supplementation mitigated pain sensitivity in DNP-treated animals. Principal component analysis showed that GEG treatment shifts the microbiome profile from control and DNP samples. Although GEG did not alter the richness of the microbiome, it significantly increased the alpha-diversity in terms of evenness in comparison to DNP (P < 0.05). Using Kruskal–Wallis test followed by the post-hoc Dunn’s test, we identified 9 specific taxa, and their abundance was significantly altered among the control, DNP, and DNP + GEG groups (P < 0.05). In comparison to the control group, the DNP group reduced the relative abundance of Eubacterium coprostanoligenes, Lachnospiraceae, Oscillospiraceae, and Peptococcceae, while DNP increased the abundance of Muribaculum intestinale. Relative to DNP group, the DNP + GEG treatment reversed DNP’s effect and reduced the abundance of Muribaculum intestinale to a level similar to the control group. GEG treatment increased the abundance of Acinetobacter, Azospirillum, Colidextribacter, and Fournierella. ConclusionsThis study demonstrated that GEG supplementation not only reduced pain but also favored the composition of gut microbiome in the DNP model, suggesting targeting gut microbiota by GEG may represent a new therapeutic strategy for the management of DNP. Funding SourcesTexas Tech University Health Sciences Center.