Safaa K Mohammed1, Yosra M Magdy2, Dalia Aa El-Waseef3, Enas S Nabih4, Mohamed A Hamouda5, Omnyah A El-Kharashi6. 1. Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: safaalm@hotmail.com. 2. Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: Y_yosra@outlook.com. 3. Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: daliaalaaelwaseef@gmail.com. 4. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: enassamer@hotmail.com. 5. Student at Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: hamouda_555@hotmail.com. 6. Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: omnyah2011@gmail.com.
Abstract
BACKGROUND AND AIM: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND AIM: 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. METHODOLOGY: 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. RESULTS: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. CONCLUSIONS: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.
Authors: Wen Tang; Zhaoyou Meng; Ning Li; Yiyan Liu; Li Li; Dongfeng Chen; Yang Yang Journal: Front Cell Infect Microbiol Date: 2021-01-27 Impact factor: 5.293
Authors: Amir Reza Moravejolahkami; Mohammad Ali Hojjati Kermani; Zakiyeh Balouch Zehi; Seyed Mohammad Sadegh Mirenayat; Marjan Mansourian Journal: J Diabetes Metab Disord Date: 2021-02-23