Rahman Ziaur, Padhy Hara Prasad, Dandekar Manoj P
Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, PIN 500037, Telangana, India.
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India.
Probiotics Antimicrob Proteins. 2024 Apr 24. doi: 10.1007/s12602-024-10256-w.
The beneficial effects of probiotics, postbiotics, and paraprobiotics have already been registered in managing ischemic stroke-generated neuroinflammation and gut dysbiosis. Herein, we examined the impact of cell-free supernatant (CFS) obtained from probiotics (Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01) in a rat transient middle cerebral artery occlusion (MCAO) model of focal cerebral injury. Pre-MCAO supplementation of probiotics (2 × 10 CFU/mL) for 21 days or CFS (1 mL/rat) for 7 days protect the MCAO-induced somatosensory and motor impairments recorded at 24 h and 72 h after reperfusion in foot-fault, rotarod, adhesive removal, and vibrissae-evoked forelimb placing tests. We also noted the reduced infarct area and neuronal degradation in the right hemisphere of probiotics- and CFS-recipient MCAO-operated animals. Moreover, MCAO-induced altered concentrations of glial-fibrillary acidic protein, NeuN, zonula occludens-1 (ZO-1), TLR4, IL-1β, IL-6, and TNF-α, as well as matrix metalloproteinase-9 (MMP9) were reversed in the treatment groups. Probiotics and CFS treatment ameliorated the elevated levels of IL-6, IL-1β, and MMP9 in the blood plasma of rats. The disrupted microbial phyla, Firmicutes-to-Bacteroides ratio, villi/crypt ratio, and decreased mucin-producing goblet cells, ZO-1, and occludin in the colon of MCAO-operated rats were recovered following probiotics and CFS treatment. NMR characterization of CFS and rat blood plasma revealed the presence of several important bacterial metabolites. These findings suggest that the CFS obtained from Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01 has the propensity to improve MCAO-generated neurological dysfunctions in rats by dampening neuroinflammation and modulating the gut-brain axis modulators.
益生菌、后生元及副益生菌在治疗缺血性中风引发的神经炎症和肠道菌群失调方面的有益作用已得到证实。在此，我们在大鼠局灶性脑损伤的短暂性大脑中动脉闭塞（MCAO）模型中，研究了从益生菌（鼠李糖乳杆菌UBLR - 58和短双歧杆菌UBBr - 01）获得的无细胞上清液（CFS）的影响。在MCAO前补充益生菌（2×10⁹CFU/mL）21天或CFS（1 mL/只大鼠）7天，可保护在再灌注后24小时和72小时在足部错误、转棒、黏附去除和触须诱发前肢放置试验中记录到的MCAO诱导的体感和运动障碍。我们还注意到，接受益生菌和CFS的MCAO手术动物右半球的梗死面积减小，神经元降解减少。此外，治疗组逆转了MCAO诱导的胶质纤维酸性蛋白、NeuN、紧密连接蛋白 - 1（ZO - 1）、Toll样受体4（TLR4）、白细胞介素 - 1β（IL - 1β）、白细胞介素 - 6（IL - 6）和肿瘤坏死因子 - α（TNF - α）以及基质金属蛋白酶 - 9（MMP9）浓度的改变。益生菌和CFS治疗改善了大鼠血浆中IL - 6、IL - 1β和MMP9升高的水平。在益生菌和CFS治疗后，MCAO手术大鼠结肠中被破坏的微生物门类、厚壁菌门与拟杆菌门的比例、绒毛/隐窝比例以及产生黏蛋白的杯状细胞、ZO - 1和闭合蛋白的减少均得到恢复。CFS和大鼠血浆的核磁共振表征显示存在几种重要的细菌代谢产物。这些发现表明，从鼠李糖乳杆菌UBLR - 58和短双歧杆菌UBBr - 01获得的CFS有通过减轻神经炎症和调节肠 - 脑轴调节剂来改善大鼠MCAO产生的神经功能障碍的倾向。
