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

A Multi-omits Approach to Unraveling the Microbiome-Mediated Effects of Arabinoxylan Oligosaccharides in Overweight Humans
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DOI:
10.1128/msystems.00209-19
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发表时间:
2019-07-01
期刊:
影响因子:
6.4
通讯作者:
Sanz, Yolanda
Sanz, Yolanda
中科院分区:
生物学2区
文献类型:
--
作者:
Benitez-Paez, Alfonso;Kjlbaek, Louise;Sanz, Yolanda

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长期摄入膳食纤维通常被认为对体重管理和新陈代谢健康有益,但干预的结果因所涉及的膳食纤维类型而有很大差异。这项研究在一项人体干预试验中对一种特定的膳食纤维的效果进行了全面的评估,该膳食纤维由富含阿拉伯木聚糖-低聚糖(Axos)的小麦麸皮提取物组成。一项综合的多项省略分析已经被用来评估一项干预试验对具有代谢综合征指数的超重个体的效果。微生物组分析通过粪便中的鸟枪式DNA测序;使用核磁共振在粪便、尿液和血浆样本中的深度代谢组学;以及在粪便和血清/血浆样本中使用质谱仪进行大量的脂谱分析。除了它们的双叉作用外,我们还观察到Axos增加了Prevoella物种的比例。元基因组分析显示,由于摄入Axos,参与维生素/辅因子产生、多糖代谢和神经递质生物合成的细菌基因的存在增加。此外,脂质组学分析显示血浆神经酰胺水平降低。最后,我们观察了普氏杆菌丰度与粪便中短链脂肪酸(SCFAs)和琥珀酸浓度之间的关系,并确定了真细菌对代谢性疾病的潜在保护作用,因为它的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。元基因组学、脂质组学和代谢组学的数据集成表明,持续摄入Axos会协调肠道微生物组和宿主代谢的各种变化,这些变化共同影响葡萄糖的动态平衡。(这项研究已在ClinicalTrials.gov注册,编号为NCT02215343。)鉴于其成本效益和临床试验显示的积极结果,使用膳食纤维食品补充剂作为减轻饮食相关疾病负担的策略的重要性是一个研究问题。对有代谢综合征迹象的超重受试者的不同生物样本进行的多项省略评估,揭示了短期摄入Axos对肠道微生物区系和宿主代谢的早期和不太明显的影响。我们观察到Axos对肠道微生物区系的深刻影响超出了它们已知的双歧作用,它同时促进了丁酸盐生产商和Prevotea Copri的广泛多样性,Prevotea Copri是一种在非西化人口中丰富的微生物物种,具有传统的生活方式和富含新鲜未加工食品的饮食。对数百种代谢物的综合评估揭示了服用Axos的新好处,如降低血浆神经酰胺水平。在全球范围内,我们观察到,Axos摄入的多种影响似乎在逆转葡萄糖稳态损害方面汇聚在一起。
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-omits 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 Prevotella 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 Prevotella abundance and short-chain fatty acids (SCFAs) and succinate concentration in feces and identified a potential protective role of Eubacterium rectale 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.)IMPORTANCE 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-omits 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 Prevotella copri, 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.