The dynamics of the gut microbiota in prediabetes during a four-year follow-up among European patients-an IMI-DIRECT prospective study.

IF 10.4 1区 生物学 Q1 GENETICS & HEREDITY
Liwei Lyu, Yong Fan, Josef Korbinian Vogt, Marc Clos-Garcia, Amelie Bonnefond, Helle Krogh Pedersen, Avirup Dutta, Robert Koivula, Sapna Sharma, Kristine Højgaard Allin, Caroline Brorsson, Henna Cederberg, Elizaveta Chabanova, Federico De Masi, Emmanouil Dermitzakis, Petra J Elders, Marieke T Blom, Monika Hollander, Rebeca Eriksen, Ian Forgie, Gary Frost, Giuseppe N Giordano, Harald Grallert, Mark Haid, Tue Haldor Hansen, Bernd Jablonka, Tarja Kokkola, Anubha Mahajan, Andrea Mari, Timothy J McDonald, Petra B Musholt, Imre Pavo, Cornelia Prehn, Martin Ridderstråle, Hartmut Ruetten, Leen M 't Hart, Jochen M Schwenk, Evelina Stankevic, Henrik S Thomsen, Jagadish Vangipurapu, Henrik Vestergaard, Ana Viñuela, Mark Walker, Torben Hansen, Allan Linneberg, Henrik Bjørn Nielsen, Søren Brunak, Mark I McCarthy, Philippe Froguel, Jerzy Adamski, Paul W Franks, Marku Laakso, Joline W J Beulens, Ewan Pearson, Oluf Pedersen
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引用次数: 0

Abstract

Background: Previous case-control studies have reported aberrations of the gut microbiota in individuals with prediabetes. The primary objective of the present study was to explore the dynamics of the gut microbiota of individuals with prediabetes over 4 years with a secondary aim of relating microbiota dynamics to temporal changes of metabolic phenotypes.

Methods: The study included 486 European patients with prediabetes. Gut microbiota profiling was conducted using shotgun metagenomic sequencing and the same bioinformatics pipelines at study baseline and after 4 years. The same phenotyping protocols and core laboratory analyses were applied at the two timepoints. Phenotyping included anthropometrics and measurement of fasting plasma glucose and insulin levels, mean plasma glucose and insulin under an oral glucose tolerance test (OGTT), 2-h plasma glucose after an OGTT, oral glucose insulin sensitivity index, Matsuda insulin sensitivity index, body mass index, waist circumference, and systolic and diastolic blood pressure. Measures of the dynamics of bacterial microbiota were related to concomitant changes in markers of host metabolism.

Results: Over 4 years, significant declines in richness were observed in gut bacterial and viral species and microbial pathways accompanied by significant changes in the relative abundance and the genetic composition of multiple bacterial species. Additionally, bacterial-viral interactions diminished over time. Despite the overall reduction in bacterial richness and microbial pathway richness, 80 dominant core bacterial species and 78 core microbial pathways were identified at both timepoints in 99% of the individuals, representing a resilient component of the gut microbiota. Over the same period, individuals with prediabetes exhibited a significant increase in glycemia and insulinemia alongside a significant decline in insulin sensitivity. Estimates of the gut bacterial microbiota dynamics were significantly correlated with temporal impairments in host metabolic health.

Conclusions: In this 4-year prospective study of European patients with prediabetes, the gut microbiota exhibited major changes in taxonomic composition, bacterial species genetics, and microbial functional potentials, many of which paralleled an aggravation of host metabolism. Whether the temporal gut microbiota changes represent an adaptation to the progression of metabolic abnormalities or actively contribute to these in prediabetes cases remains unsettled.

Trial registration: The Diabetes Research on Patient Stratification (DIRECT) study, an exploratory observational study initiated on October 15, 2012, was registered on ClinicalTrials.gov under the number NCT03814915.

一项IMI-DIRECT前瞻性研究:欧洲糖尿病患者4年随访期间肠道微生物群的动态变化
背景:以前的病例对照研究已经报道了糖尿病前期患者肠道微生物群的畸变。本研究的主要目的是探索4年以上糖尿病前期患者肠道微生物群的动态,次要目的是将微生物群动态与代谢表型的时间变化联系起来。方法:研究对象为486例欧洲糖尿病前期患者。在研究基线和4年后,使用霰弹枪宏基因组测序和相同的生物信息学管道进行肠道微生物群分析。在两个时间点采用相同的表型方案和核心实验室分析。表型包括人体测量和空腹血糖和胰岛素水平的测量,口服葡萄糖耐量试验(OGTT)下的平均血糖和胰岛素,OGTT后2小时血浆血糖,口服葡萄糖胰岛素敏感性指数,松田胰岛素敏感性指数,体重指数,腰围,收缩压和舒张压。细菌微生物群的动态测量与宿主代谢标志物的伴随变化有关。结果:在4年的时间里,肠道细菌、病毒种类和微生物途径的丰富度显著下降,多种细菌种类的相对丰度和遗传组成也发生了显著变化。此外,细菌-病毒的相互作用随着时间的推移而减弱。尽管细菌丰富度和微生物途径丰富度总体下降,但99%的个体在两个时间点都鉴定出80种优势核心细菌物种和78种核心微生物途径,代表了肠道微生物群的弹性组成部分。在同一时期,糖尿病前期患者表现出血糖和胰岛素血症显著增加,同时胰岛素敏感性显著下降。肠道细菌微生物群动态的估计与宿主代谢健康的时间损伤显着相关。结论:在这项对欧洲糖尿病前期患者进行的为期4年的前瞻性研究中,肠道微生物群在分类组成、细菌种类遗传学和微生物功能潜力方面发生了重大变化,其中许多变化与宿主代谢的加剧有关。在前驱糖尿病患者中,肠道菌群的变化是否代表了对代谢异常进展的适应,还是积极地促进了代谢异常进展,目前仍未定论。试验注册:糖尿病患者分层研究(DIRECT)是一项探索性观察性研究,于2012年10月15日启动,已在ClinicalTrials.gov上注册,编号为NCT03814915。
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来源期刊
Genome Medicine
Genome Medicine GENETICS & HEREDITY-
CiteScore
20.80
自引率
0.80%
发文量
128
审稿时长
6-12 weeks
期刊介绍: Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.
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