State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.
School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.
J Agric Food Chem. 2023 Jun 14;71(23):8877-8893. doi: 10.1021/acs.jafc.2c07606. Epub 2023 Jun 2.
Parkinson's disease (PD) is closely linked to lifestyle factors, particularly dietary patterns, which have attracted interest as potential disease-modifying factors. Eating a low-protein, high-carbohydrate (LPHC) diet is a promising dietary intervention against brain aging; however, its protective effect on PD remains elusive. Here, we found that an LPHC diet ameliorated 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced motor deficits, decreased dopaminergic neuronal death, and increased the levels of striatal dopamine, serotonin, and their metabolites in PD mice. Levels of fibroblast growth factor 21 (FGF-21), a member of the fibroblast growth factor family, were elevated in PD mice following LPHC treatment. Furthermore, the administration of FGF-21 exerted a protective effect on MPTP-induced PC12 cells, similar to the effect of an LPHC diet in MPTP-induced mice. Sequencing of the 16S rDNA from fecal microbiota revealed that an LPHC diet normalized the gut bacterial composition imbalance in PD mice, as evidenced by the increased abundance of the genera , , , and and decreased abundance of , and . PICRUSt-predicted fecal microbiome function revealed that an LPHC diet suppressed lipopolysaccharide biosynthesis and the citrate cycle (TCA cycle), biosynthesis of ubiquinone and other terpenoid-quinones, and oxidative phosphorylation pathways caused by MPTP, and enhanced the biosynthesis of amino acids, carbohydrate metabolism, and biosynthesis of other secondary metabolites. A nonmetabolomic analysis of the serum and feces showed that an LPHC diet significantly increased the levels of aromatic amino acids (AAAs), including tryptophan, tyrosine, and phenylalanine. In addition, an LPHC diet elevated the serum concentrations of bile acids (BAs), particularly tauroursodeoxycholic acid (TUDCA) and taurine. Collectively, our current findings point to the potential mechanism of administering an LPHC diet in attenuating movement impairments in MPTP-induced PD mice, with AAAs, microbial metabolites (TUDCA and taurine), and FGF-21 as key mediators along the gut-microbiota-brain axis.
帕金森病（PD）与生活方式因素密切相关，特别是饮食模式，它们作为潜在的疾病修饰因素引起了人们的兴趣。低蛋白、高碳水化合物（LPHC）饮食是一种有前途的对抗大脑衰老的饮食干预措施；然而，其对 PD 的保护作用仍不清楚。在这里，我们发现 LPHC 饮食改善了 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的运动障碍，减少了多巴胺能神经元死亡，并增加了 PD 小鼠纹状体多巴胺、血清素及其代谢物的水平。成纤维细胞生长因子 21（FGF-21）是成纤维细胞生长因子家族的成员，在 LPHC 治疗后，PD 小鼠的 FGF-21 水平升高。此外，FGF-21 的给药对 MPTP 诱导的 PC12 细胞具有保护作用，类似于 LPHC 饮食在 MPTP 诱导的小鼠中的作用。粪便 16S rDNA 测序显示，LPHC 饮食使 PD 小鼠的肠道细菌组成失衡正常化，这表现为属的丰度增加、、、和减少、和。PICRUSt 预测的粪便微生物组功能表明，LPHC 饮食抑制了 LPS 生物合成和柠檬酸循环（TCA 循环）、泛醌和其他萜烯醌的生物合成以及由 MPTP 引起的氧化磷酸化途径，并增强了氨基酸、碳水化合物代谢和其他次生代谢物的生物合成。血清和粪便的非代谢组学分析表明，LPHC 饮食显著增加了芳香族氨基酸（AAAs）的水平，包括色氨酸、酪氨酸和苯丙氨酸。此外，LPHC 饮食提高了血清中胆汁酸（BAs）的浓度，特别是牛磺熊脱氧胆酸（TUDCA）和牛磺酸。总的来说，我们目前的发现表明，在 MPTP 诱导的 PD 小鼠中，LPHC 饮食可能通过 AAAs、微生物代谢物（TUDCA 和牛磺酸）和 FGF-21 作为关键介质来减轻运动障碍，这些介质沿着肠道-微生物群-大脑轴发挥作用。
