Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Obesity Research Institute, Texas Tech University, Lubbock, TX, USA.
Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Nutr Res. 2024 Apr;124:73-84. doi: 10.1016/j.nutres.2024.01.014. Epub 2024 Feb 1.
The relationship among gut microbiota, mitochondrial dysfunction/neuroinflammation, and diabetic neuropathic pain (DNP) has received increased attention. Ginger has antidiabetic and analgesic effects because of its anti-inflammatory property. We examined the effects of gingerols-enriched ginger (GEG) supplementation on pain-associated behaviors, gut microbiome composition, and mitochondrial function and neuroinflammation of colon and spinal cord in DNP rats. Thirty-three male rats were randomly divided into 3 groups: control group, DNP group (high-fat diet plus single dose of streptozotocin at 35 mg/kg body weight, and GEG group (DNP+GEG at 0.75% in the diet for 8 weeks). Von Frey and open field tests were used to assess pain sensitivity and anxio-depressive behaviors, respectively. Colon and spinal cord were collected for gene expression analysis. 16S rRNA gene sequencing was done from cecal samples and microbiome data analysis was performed using QIIME 2. GEG supplementation mitigated mechanical hypersensitivity and anxio-depressive behavior in DNP animals. GEG supplementation suppressed the dynamin-related protein 1 protein expression (colon) and gene expression (spinal cord), astrocytic marker GFAP gene expression (colon and spinal cord), and tumor necrosis factor-α gene expression (colon, P < .05; spinal cord, P = .0974) in DNP rats. GEG supplementation increased microglia/macrophage marker CD11b gene expression in colon and spinal cord of DNP rats. GEG treatment increased abundance of Acinetobacter, Azospirillum, Colidextribacter, and Fournierella but decreased abundance of Muribaculum intestinale in cecal feces of rats. This study demonstrates that GEG supplementation decreased pain, anxio-depression, and neuroimmune cells, and improved the composition of gut microbiomes and mitochondrial function in rats with diabetic neuropathy.
肠道微生物群、线粒体功能障碍/神经炎症与糖尿病性神经病理性疼痛（DNP）之间的关系受到了越来越多的关注。生姜具有抗炎作用，因此具有降血糖和镇痛作用。我们研究了姜辣素富集生姜（GEG）补充对 DNP 大鼠疼痛相关行为、肠道微生物群组成以及结肠和脊髓中线粒体功能和神经炎症的影响。33 只雄性大鼠随机分为 3 组：对照组、DNP 组（高脂肪饮食加 35mg/kg 体重的链脲佐菌素单次注射）和 GEG 组（DNP+GEG 组，饮食中添加 0.75%的 GEG 持续 8 周）。von Frey 和旷场试验分别用于评估疼痛敏感性和焦虑-抑郁行为。收集结肠和脊髓进行基因表达分析。对盲肠样本进行 16S rRNA 基因测序，并使用 QIIME 2 进行微生物组数据分析。GEG 补充缓解了 DNP 动物的机械性高敏和焦虑-抑郁行为。GEG 补充抑制了 DNP 大鼠的动力蛋白相关蛋白 1 蛋白表达（结肠）和基因表达（脊髓）、星形胶质细胞标志物 GFAP 基因表达（结肠和脊髓）和肿瘤坏死因子-α基因表达（结肠，P<0.05；脊髓，P=0.0974）。GEG 补充增加了 DNP 大鼠结肠和脊髓中微胶质细胞/巨噬细胞标志物 CD11b 基因的表达。GEG 治疗增加了盲肠粪便中不动杆菌属、固氮螺菌属、科莱德克斯杆菌属和福氏耐格里菌属的丰度，但降低了肠道微生物属 Muribaculum intestinale 的丰度。本研究表明，GEG 补充可减少疼痛、焦虑-抑郁和神经免疫细胞，并改善糖尿病神经病变大鼠的肠道微生物群组成和线粒体功能。
