BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA ...BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.METHODS Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were collected.Following fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™system.RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides distasonis.The functional prediction provided two different metabolic profiles between MASLD and LOLA.The 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis.The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.展开更多
目的评价L-鸟氨酸-L-门冬氨酸(LOLA)治疗肝硬化肝性脑病(HE)的疗效和安全性。方法计算机检索MEDLINE、PubMed、EMBase、The Cochrane Central Register of Controlled Trials、中国生物医学文献数据库、中国科技期刊数据库(维普)、中国...目的评价L-鸟氨酸-L-门冬氨酸(LOLA)治疗肝硬化肝性脑病(HE)的疗效和安全性。方法计算机检索MEDLINE、PubMed、EMBase、The Cochrane Central Register of Controlled Trials、中国生物医学文献数据库、中国科技期刊数据库(维普)、中国期刊全文数据库和万方数字化期刊全文数据库。中文检索词为:L-鸟氨酸-L-门冬氨酸、肝硬化、肝性脑病、随机对照试验;英文检索词为:L-ornithine-L-aspartate,hepatic cirrhosis,hepaticencephalopathy,randomized controlled trial。检索LOLA治疗肝硬化HE的临床随机对照试验,采用Cochrane图书馆提供的Review Manager 3.4软件对纳入的研究进行Meta分析。结果共纳入6项研究,包括512例肝硬化HE患者。纳入研究的主要结局指标有:(1)疾病临床缓解率;(2)血氨值;(3)缩短数字连接试验A(NCT-A)反应时间;(4)药物不良反应发生情况。纳入研究的Jadad评分为3～5分,均为高质量临床随机对照研究。Meta分析结果显示:(1)LOLA组HE临床缓解率高于对照组〔RR=1.49,95%CI(1.10,2.01),P=0.010〕;亚组分析结果显示,LOLA组轻微肝性脑病(MHE)临床缓解率高于对照组〔RR=2.25,95%CI(1.33,3.82),P=0.003〕,显性肝性脑病(OHE)临床缓解率也高于对照组〔RR=1.31,95%CI(1.15,1.50),P<0.0001〕。(2)LOLA组血氨值下降程度大于对照组〔WMD=-10.22,95%CI(-13.70,-6.75),P<0.00001〕。(3)LOLA组NCT-A反应时间短于对照组〔WMD=-10.34,95%CI(-14.87,-5.80),P<0.00001〕。(4)LOLA组药物不良反应发生率(13.0%)低于对照组(10.6%)〔RR=1.22,95%CI(0.69,2.17),P=0.49〕。结论现有的临床研究证据表明,LOLA可提高肝硬化HE患者疾病临床缓解率,对MHE和OHE同样有效,可明显降低肝硬化HE患者血氨水平,缩短NCT-A反应时间,且不良反应发生率低、疗效肯定、安全性好。展开更多
基金Financiamento e IncentivoàPesquisa from Hospital de Clínicas de Porto Alegre(FIPE/HCPA),No.2020-0037Coordination for the Improvement of Higher Education Personnel,CAPES/PNPDand the Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq).
文摘BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.METHODS Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were collected.Following fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™system.RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides distasonis.The functional prediction provided two different metabolic profiles between MASLD and LOLA.The 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis.The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.
