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采用系统生物学方法研究病态肥胖患者的肠道微生物群和宿主代谢:BARIA 纵向队列研究的设计。

A systems biology approach to understand gut microbiota and host metabolism in morbid obesity: design of the BARIA Longitudinal Cohort Study.

机构信息

From the, Department of Vascular Medicine, Amsterdam UMC, Amsterdam, The Netherlands.

Department of Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, The Netherlands.

出版信息

J Intern Med. 2021 Mar;289(3):340-354. doi: 10.1111/joim.13157. Epub 2020 Sep 29.

DOI:10.1111/joim.13157
PMID:32640105
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7984244/
Abstract

INTRODUCTION

Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples.

METHODS

The BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling. Patient follow-up will be ten years.

RESULTS

Preoperative MMT of 170 patients were analysed and clear differences were observed in glucose homeostasis between individuals. Repeated MMT in 10 patients showed satisfactory intra-individual reproducibility, with differences in plasma glucose, insulin and triglycerides within 20% of the mean difference.

CONCLUSION

The BARIA study can add more understanding in how gut-microbiota affect metabolism, especially with regard to obesity, glucose metabolism and NAFLD. Identification of key factors may provide diagnostic and therapeutic leads to control the obesity-associated disease epidemic.

摘要

简介

肥胖及其相关疾病(包括 2 型糖尿病、血脂异常和非酒精性脂肪性肝病[NAFLD])的患病率正在上升。其潜在机制,尤其是在人类中,尚不清楚。减重手术为获得活检和门静脉血样提供了独特的机会。

方法

BARIA 研究旨在评估微生物群及其代谢物如何影响肥胖患者关键组织中的转录和临床结局,以及基线人体测量学和代谢特征如何决定减重手术后的体重减轻和葡萄糖稳态。我们对接受减重手术(主要是腹腔镜 Roux-en-Y 胃旁路术)的患者进行表型分析,在减肥前,使用生物计量学、饮食和心理问卷、混合餐测试(MMT)收集粪便样本和术中取自肝脏、脂肪组织和空肠的活检。我们的目标是纳入 1500 名患者。其中一部分(约 25%)将接受术中门静脉采血。分析粪便样本的 shotgun 宏基因组学和靶向代谢组学,空腹和餐后血浆样本进行代谢组学分析,从组织中提取 RNA 进行 RNAseq 分析。数据将使用最先进的神经元网络和代谢建模进行整合。患者随访时间为十年。

结果

分析了 170 例患者的术前 MMT,观察到个体间葡萄糖稳态存在明显差异。10 例患者的重复 MMT 显示出良好的个体内可重复性,血浆葡萄糖、胰岛素和甘油三酯的差异在平均差异的 20%以内。

结论

BARIA 研究可以进一步了解肠道微生物群如何影响代谢,特别是在肥胖、葡萄糖代谢和 NAFLD 方面。确定关键因素可能为控制肥胖相关疾病流行提供诊断和治疗线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0bc/7984244/2ad455992a64/JOIM-289-340-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0bc/7984244/39c608d2caaa/JOIM-289-340-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0bc/7984244/ab245f10384e/JOIM-289-340-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0bc/7984244/9df028686685/JOIM-289-340-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0bc/7984244/2ad455992a64/JOIM-289-340-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0bc/7984244/39c608d2caaa/JOIM-289-340-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0bc/7984244/ab245f10384e/JOIM-289-340-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0bc/7984244/9df028686685/JOIM-289-340-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0bc/7984244/2ad455992a64/JOIM-289-340-g002.jpg

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