Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Physiol Behav. 2020 Feb 1;214:112762. doi: 10.1016/j.physbeh.2019.112762. Epub 2019 Nov 28.
Disturbance of gut microbiota plays a role in induction and progression of non alcoholic steatohepatitis (NASH) and the associated cognitive dysfunction. We supposed that high fat diet (HFD)-induced dysbiosis may lead to NASH/cognitive impairment co-morbidities through hippocampal TLR4/BDNF signaling pathway and the regaining of microbiota balance through probiotics could provide a therapeutic option.
Four groups of male Wister rats were used; Naïve, Lactobacillus Plantarum EMCC-1039 (LP EMCC-1039), NASH and NASH+ LP EMCC-1039 groups. After induction of NASH with high fat diet (HFD), LP EMCC-1039 was given daily by oral gavage in the last two weeks of experiment to the treated group. Body weight percentage (BW%) changes, Lee index (LI), liver function tests, expression of BDNF, TLR4 with RT-PCR and quantification of BDNF, TLR4 by ELISA were measured . Histological studies and assessment of cognitive function were also performed.
NASH group showed an increase in BW% and LI . It was associated with cognitive deficits, an increase in hepatic, hippocampal TLR4 expression and decline in BDNF expression and protein, all p values were <0.05. Histological examination revealed significant decrease in number of viable cells and shrinking of pyramidal cells in hippocampus (p<0.05). Treatment with LP EMCC-1039 improved all these pathological changes significantly (p<0.05) with negative correlation between NAFLD activity score (NAS) and cognitive measurements. Additionally, hepatic and hippocampal TLR4 expression were decreased and BDNF expression and quantity were increased.
Dysbiosis-induced NASH was associated with cognitive impairment and a probiotic (LP EMCC-1039) supplementation has beneficial effect through modulation of TLR4/BDNF signaling pathway.
肠道微生物群的紊乱在非酒精性脂肪性肝炎（NASH）的诱导和进展以及相关认知功能障碍中发挥作用。我们假设高脂肪饮食（HFD）诱导的生态失调可能通过海马 TLR4/BDNF 信号通路导致 NASH/认知障碍合并症，而通过益生菌恢复微生物群平衡可能提供一种治疗选择。
使用四组雄性 Wister 大鼠；天真组、植物乳杆菌 EMCC-1039（LP EMCC-1039）组、NASH 组和 NASH+LP EMCC-1039 组。在用高脂肪饮食（HFD）诱导 NASH 后，在实验的最后两周内通过口服灌胃给予治疗组 LP EMCC-1039。测量体重百分比（BW%）变化、Lee 指数（LI）、肝功能试验、BDNF、TLR4 的表达，通过 RT-PCR 和 ELISA 定量 BDNF、TLR4。还进行了组织学研究和认知功能评估。
NASH 组 BW%和 LI 增加。它与认知缺陷、肝、海马 TLR4 表达增加以及 BDNF 表达和蛋白减少有关，所有 p 值均<0.05。组织学检查显示海马中存活细胞数量显着减少和锥体细胞缩小（p<0.05）。用 LP EMCC-1039 治疗显着改善了所有这些病理变化（p<0.05），NAFLD 活动评分（NAS）与认知测量呈负相关。此外，肝和海马 TLR4 表达减少，BDNF 表达和数量增加。
生态失调诱导的 NASH 与认知障碍有关，益生菌（LP EMCC-1039）补充通过调节 TLR4/BDNF 信号通路具有有益作用。
