Centro de Referencia para Lactobacilos (CERELA-CONICET), Chacabuco 145, San Miguel de Tucumán,, T4000ILC, Tucumán, Argentina.
Neurochem Res. 2024 Oct;49(10):2940-2956. doi: 10.1007/s11064-024-04217-6. Epub 2024 Aug 1.
Alterations of the microbiota-gut-brain axis has been associated with intestinal and neuronal inflammation in Parkinson's disease (PD). The aim of this work was to study some mechanisms associated with the neuroprotective effect of a combination (MIX) of lactic acid bacteria (LAB) composed by Lactiplantibacillus plantarum CRL2130 (riboflavin overproducing strain), Streptococcus thermophilus CRL808 (folate producer strain), and CRL807 (immunomodulatory strain) in cell cultures and in a chronic model of parkinsonism induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in aged mice, and under levodopa-benserazide treatment. In vitro, N2a differentiated neurons were exposed to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and treated with intracellular bacterial extracts or with conditioned media from BV-2 cells exposed to the bacterial extracts. In vivo, motor skills, tyrosine hydrolase (TH) in brain and cytokine concentrations in serum and in brain were evaluated. The study of the faecal microbiota and the histology of the small intestine was also performed. The results showed that the neuroprotective effect associated with LAB MIX administration did not interfere with levodopa-benserazide treatment. This effect could be associated with the antioxidant and immunomodulatory potential of the LAB selected in the MIX, and was associated with the significant improvement in the motor tests and a higher number of TH + cells in the brain. In addition, LAB MIX administration was associated with modulation of the immune response. LAB administration decreased intestinal damage with an increase in the villus length /crypt depth ratio. Finally, the administration of the LAB MIX in combination with levodopa-benserazide treatment was able to partially revert the intestinal dysbiosis observed in the model, showing greater similarity to the profiles of healthy controls, and highlighting the increase in the Lactobacillaceae family. Different mechanisms of action would be related to the protective effect of the selected LAB combination which has the potential to be evaluated as an adjuvant for conventional PD therapies.
微生物群-肠道-大脑轴的改变与帕金森病 (PD) 中的肠道和神经元炎症有关。本工作的目的是研究与乳酸杆菌 (LAB) 组合 (MIX) 的神经保护作用相关的一些机制，该组合由植物乳杆菌 CRL2130（核黄素高产菌株）、嗜热链球菌 CRL808（叶酸产生菌株）和 CRL807（免疫调节菌株）组成，用于细胞培养和在衰老小鼠中用 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 诱导的慢性帕金森病模型中，并在左旋多巴-卡比多巴治疗下。在体外，将分化的 N2a 神经元暴露于神经毒素 1-甲基-4-苯基吡啶 (MPP+)，并用细胞内细菌提取物或暴露于细菌提取物的 BV-2 细胞的条件培养基处理。在体内，评估运动技能、大脑中的酪氨酸羟化酶 (TH) 和血清及大脑中的细胞因子浓度。还进行了粪便微生物群的研究和小肠的组织学检查。结果表明，LAB MIX 给药的神经保护作用与左旋多巴-卡比多巴治疗不干扰。这种作用可能与所选 LAB 在 MIX 中的抗氧化和免疫调节潜力有关，并且与运动测试的显著改善以及大脑中更多的 TH+细胞有关。此外，LAB MIX 给药与免疫反应的调节有关。LAB 给药减少了肠道损伤，增加了绒毛长度/隐窝深度比。最后，LAB MIX 与左旋多巴-卡比多巴联合给药能够部分逆转模型中观察到的肠道失调，使其与健康对照组的谱更相似，并突出了乳杆菌科家族的增加。不同的作用机制与选定的 LAB 组合的保护作用有关，该组合有可能作为常规 PD 治疗的辅助剂进行评估。
