在饮食诱发的肥胖小鼠中，GLP-1或双重GLP-1 / GLP-2受体激动剂治疗后，代谢和肠道微生物组发生变化。,Scientific Reports

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在饮食诱发的肥胖小鼠中，GLP-1或双重GLP-1 / GLP-2受体激动剂治疗后，代谢和肠道微生物组发生变化。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-10-30 , DOI: 10.1038/s41598-019-52103-x
Mette Simone Aae Madsen _{1,

2} , Jacob Bak Holm ₃ , Albert Pallejà ₃ , Pernille Wismann ₁ , Katrine Fabricius ₁ , Kristoffer Rigbolt ₁ , Martin Mikkelsen ₁ , Morten Sommer ₂ , Jacob Jelsing ₁ , Henrik Bjørn Nielsen ₃ , Niels Vrang ₁ , Henrik H Hansen ₁

Affiliation

肠内分泌L细胞衍生的肽激素，特别是胰高血糖素样肽1（GLP-1）和胰高血糖素样肽2（GLP-2），已成为治疗2型糖尿病，肥胖症和肠道疾病的重要靶标。由于肠道微生物失衡和适应不良的宿主反应与肥胖和糖尿病的病理学有关，因此本研究旨在确定药理刺激的GLP-1和GLP-2受体功能对饮食诱发的肥胖（DIO）中肠道微生物组组成的影响）老鼠。DIO小鼠接受了选择性GLP-1受体激动剂（利拉鲁肽，0.2 mg / kg，BID）或双重GLP-1 / GLP-2受体激动剂（GUB09-145，0.04 mg / kg，BID）治疗4周。两种化合物均抑制热量的摄入，促进体重明显减轻，葡萄糖耐量提高，血浆胆固醇水平降低。16S rDNA测序和深度测序shot弹枪宏基因组学被用于肠道微生物组特征变化的全面受试者内分析。与基线相比，DIO小鼠在利拉鲁肽和GUB09-145处理后假设系统发育相似的肠道细菌组成变化，其特征是低丰度物种和相关细菌代谢途径的离散变化。微生物组的改变可能潜在地与GLP-1和GLP-2受体信号转导对热量摄入，葡萄糖代谢和脂质处理的聚合生物学作用有关。在利拉鲁肽和GUB09-145处理后，DIO小鼠假定在系统发育上与肠道细菌组成相似，其特征是低丰度物种和相关细菌代谢途径的离散变化。微生物组的改变可能潜在地与GLP-1和GLP-2受体信号转导对热量摄入，葡萄糖代谢和脂质处理的聚合生物学作用有关。在利拉鲁肽和GUB09-145处理后，DIO小鼠假定在系统发育上与肠道细菌组成相似，其特征是低丰度物种和相关细菌代谢途径的离散变化。微生物组的改变可能潜在地与GLP-1和GLP-2受体信号转导对热量摄入，葡萄糖代谢和脂质处理的聚合生物学作用有关。

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Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice.

Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09-145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.

更新日期：2019-10-30

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