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OBJECTIVES: Diabetic 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. METHODS: Thirty-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. RESULTS: Relative 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

OBJECTIVES: Emerging evidence has suggested that gut microbiota plays a key role during the development of chronic pain, such as neuropathic pain (NP). This study was to evaluate the effects of two ginger root extract isomers (gingerols and shogaols) on the composition and function of gut microbiota in animals with NP. METHODS: Sixteen male Sprague-Dawley rats were randomly assigned into 4 groups: sham group, spinal nerve ligation (SNL) group as the pain control group, SNL + gingerols-enriched ginger (GEG) extract group, and SNL + shogaols-enriched ginger (SEG) extract group. Animals in GEG and SEG groups were fed their respective diets on the day of SNL surgery for 30 days. At day 30, fecal samples were collected for microbiota composition and functional analyses. 16S rRNA gene sequencing was conducted from fecal samples and microbiome data analysis was performed with QIIME2 and PICRUSt2. Data were analyzed using non-parametric Kruskal–Wallis test to compare GEG and SEG with SNL group. RESULTS: Based on the results of alpha-diversity analyses, neither GEG nor SEG treatment affected the evenness of microbiome. Gingerols or shogaols supplementation into the diet reduced the richness of the gut microbiome, compared to the SNL group. Relative to the SNL group, GEG group had an increase in the relative abundance of the genus Faecalitalea, while SEG group had an increase in the relative abundance of the genus Aerococcus and species Bacteroides massiliensis. In comparison to SNL group, both GEG and SEG groups showed a decrease in the relative abundance of the family Muribaculaceae and the genus Rikenellaceae RC9 gut group. Functional profiling results revealed that relative to the SNL group, both GEG and SEG supplementation increased the proportion of biosynthetic pathways related to energy metabolism (i.e., pentose phosphate pathway and sugar degradation) and peptidoglycan biosynthesis. Furthermore, GEG and SEG differentially modified amino acid-related metabolic pathways, i.e., tyrosine degradation, tryptophan biosynthesis, arginine, and ornithine biosynthesis. CONCLUSIONS: GEG and SEG exhibited differential effects on the microbiome composition and function, suggesting a prebiotic potential for dietary ginger root intake in the management of NP. FUNDING SOURCES: Texas Tech University Health Sciences Center.