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一种多组学方法用于揭示阿拉伯木聚糖寡糖对超重人群微生物组介导的影响

A Multi-omics Approach to Unraveling the Microbiome-Mediated Effects of Arabinoxylan Oligosaccharides in Overweight Humans.

作者信息

Benítez-Páez Alfonso, Kjølbæk Louise, Gómez Del Pulgar Eva M, Brahe Lena K, Astrup Arne, Matysik Silke, Schött Hans-Frieder, Krautbauer Sabrina, Liebisch Gerhard, Boberska Joanna, Claus Sandrine, Rampelli Simone, Brigidi Patrizia, Larsen Lesli H, Sanz Yolanda

机构信息

Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Paterna-Valencia, Spain

Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg C, Denmark.

出版信息

mSystems. 2019 May 28;4(4):e00209-19. doi: 10.1128/mSystems.00209-19.

DOI:10.1128/mSystems.00209-19
PMID:31138673
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6538848/
Abstract

Long-term consumption of dietary fiber is generally considered beneficial for weight management and metabolic health, but the results of interventions vary greatly depending on the type of dietary fibers involved. This study provides a comprehensive evaluation of the effects of a specific dietary fiber consisting of a wheat-bran extract enriched in arabinoxylan-oligosaccharides (AXOS) in a human intervention trial. An integrated multi-omics analysis has been carried out to evaluate the effects of an intervention trial with an AXOS-enriched diet in overweight individuals with indices of metabolic syndrome. Microbiome analyses were performed by shotgun DNA sequencing in feces; in-depth metabolomics using nuclear magnetic resonance in fecal, urine, and plasma samples; and massive lipid profiling using mass spectrometry in fecal and serum/plasma samples. In addition to their bifidogenic effect, we observed that AXOS boost the proportion of species. Metagenome analysis showed increases in the presence of bacterial genes involved in vitamin/cofactor production, glycan metabolism, and neurotransmitter biosynthesis as a result of AXOS intake. Furthermore, lipidomics analysis revealed reductions in plasma ceramide levels. Finally, we observed associations between abundance and short-chain fatty acids (SCFAs) and succinate concentration in feces and identified a potential protective role of against metabolic disease given that its abundance was positively associated with plasma phosphatidylcholine levels, thus hypothetically reducing bioavailability of choline for methylamine biosynthesis. The metagenomics, lipidomics, and metabolomics data integration indicates that sustained consumption of AXOS orchestrates a wide variety of changes in the gut microbiome and the host metabolism that collectively would impact on glucose homeostasis. (This study has been registered at ClinicalTrials.gov under identifier NCT02215343) The use of dietary fiber food supplementation as a strategy to reduce the burden of diet-related diseases is a matter of study given its cost-effectiveness and the positive results demonstrated in clinical trials. This multi-omics assessment, on different biological samples of overweight subjects with signs of metabolic syndrome, sheds light on the early and less evident effects of short-term AXOS intake on intestinal microbiota and host metabolism. We observed a deep influence of AXOS on gut microbiota beyond their recognized bifidogenic effect by boosting concomitantly a wide diversity of butyrate producers and , a microbial species abundant in non-Westernized populations with traditional lifestyle and diets enriched in fresh unprocessed foods. A comprehensive evaluation of hundreds of metabolites unveiled new benefits of the AXOS intake, such as reducing the plasma ceramide levels. Globally, we observed that multiple effects of AXOS consumption seem to converge in reversing the glucose homeostasis impairment.

摘要

长期食用膳食纤维通常被认为对体重管理和代谢健康有益,但干预结果因所涉及的膳食纤维类型而异。本研究在一项人体干预试验中,对一种富含阿拉伯木聚糖寡糖(AXOS)的麦麸提取物组成的特定膳食纤维的效果进行了全面评估。已开展综合多组学分析,以评估富含AXOS的饮食干预试验对患有代谢综合征指标的超重个体的影响。通过鸟枪法DNA测序对粪便进行微生物组分析;使用核磁共振对粪便、尿液和血浆样本进行深入代谢组学分析;并使用质谱对粪便和血清/血浆样本进行大规模脂质谱分析。除了其双歧杆菌生成作用外,我们还观察到AXOS提高了某些物种的比例。宏基因组分析表明,摄入AXOS后,参与维生素/辅因子生成、聚糖代谢和神经递质生物合成的细菌基因的存在有所增加。此外,脂质组学分析显示血浆神经酰胺水平降低。最后,我们观察到粪便中某些菌的丰度与短链脂肪酸(SCFAs)和琥珀酸浓度之间的关联,并确定了该菌对代谢疾病的潜在保护作用,因为其丰度与血浆磷脂酰胆碱水平呈正相关,从而假设降低了胆碱用于甲胺生物合成的生物利用度。宏基因组学、脂质组学和代谢组学数据整合表明,持续食用AXOS会在肠道微生物群和宿主代谢中引发多种变化,这些变化共同会影响葡萄糖稳态。(本研究已在ClinicalTrials.gov上注册,标识符为NCT02215343)鉴于膳食纤维食品补充剂的成本效益及其在临床试验中显示的积极结果,将其作为减轻饮食相关疾病负担的策略是一个研究课题。这项针对有代谢综合征迹象的超重受试者的不同生物样本的多组学评估,揭示了短期摄入AXOS对肠道微生物群和宿主代谢的早期且不太明显的影响。我们观察到,AXOS除了具有公认的双歧杆菌生成作用外,还通过同时促进多种丁酸盐产生菌以及一种在非西方化人群中丰富的微生物物种(其传统生活方式和饮食富含新鲜未加工食品)的生长,对肠道微生物群产生了深远影响。对数百种代谢物的全面评估揭示了摄入AXOS的新益处,例如降低血浆神经酰胺水平。总体而言,我们观察到食用AXOS的多种作用似乎在逆转葡萄糖稳态受损方面趋于一致。

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