背景:代谢功能障碍相关的脂肪变性肝病(MASLD)是代谢综合征的肝脏表现。研究表明鸟氨酸天冬氨酸(LOLA)作为药物治疗。
目的:利用MASLD营养模型分析LOLA摄入对肠道菌群的影响。
方法:成年雄性SpragueDawley大鼠随机分为三组:对照组(10只标准饮食喂养),MASLD(10只大鼠饲喂高脂肪和胆碱缺乏的饮食),和LOLA(10只大鼠接受200mg/kg/dLOLA,在第16周接受高脂肪和胆碱缺乏饮食后)。实验28周后,动物被安乐死,收集肠道中存在的粪便。粪便DNA提取后,扩增16SrRNA基因的V4区,然后在IonS5™系统中进行测序.
结果:Alpha和beta多样性指标在MASLD和LOLA之间具有可比性。3个OTU在MASLD和LOLA之间差异丰富,属于啮齿动物螺杆菌,金氏副杆菌,和分布式副杆菌属。功能预测在MASLD和LOLA之间提供了两种不同的代谢谱。MASLD中差异丰富的9种途径与能量来源的变化有关,腺苷/嘌呤核苷酸降解以及鸟苷和腺苷脱氧核糖核苷酸的生物合成。LOLA中差异丰富的14个途径与主要受L-天冬氨酸影响的4个主要代谢功能相关。包括三羧酸循环途径,嘌呤/鸟苷核苷酸生物合成,嘧啶核糖核苷酸的生物合成和救助以及脂质IVA的生物合成。
结论:尽管在MASLD的这种营养模型中,LOLA对α和β多样性没有影响,它与特定肠道微生物及其相关代谢途径的变化有关。
BACKGROUND: Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug therapy.
OBJECTIVE: 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.
CONCLUSIONS: 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.