PDF(Pubmed)
Abstract：
The human gut microbiota is characterized by large interpersonal differences, which are not only linked to health and disease but also determine the outcome of nutritional interventions. In line with the growing interest for developing targeted gut microbiota modulators, the selectivity of a carrot-derived rhamnogalacturonan I (cRG-I) was compared to substrates with demonstrated low (inulin, IN) and high selectivity (xanthan, XA), at a human equivalent dose (HED) of 1.5 g/d. The high throughput of the ex vivo SIFR® technology, validated to generate predictive insights for clinical findings, enabled the inclusion of 24 human adults. Such an unprecedented high number of samples in the context of in vitro gut microbiota modelling allowed a coverage of clinically relevant interpersonal differences in gut microbiota composition and function. A key finding was that cRG-I supplementation (already at an HED of 0.3 g/d) lowered interpersonal compositional differences due to the selective stimulation of taxa that were consistently present among human adults, including OTUs related to Bacteroides dorei/vulgatus and Bifidobacterium longum (suspected keystone species), Bacteroides thetaiotaomicron, Bifidobacterium adolescentis and butyrate-producing taxa such as Blautia sp., Anaerobutyricum hallii, and Faecalibacterium prausnitzii. In contrast, both IN and XA treatments increased interpersonal compositional differences. For IN, this followed from its low specificity. For XA, it was rather the extremely high selectivity of XA fermentation that caused large differences between 15 responders and 9 nonresponders, caused by the presence/absence of highly specific XA-fermenting taxa. While all test compounds significantly enhanced acetate, propionate, butyrate, and gas production, cRG-I resulted in a significantly higher acetate (+40%), propionate (+22%), yet a lower gas production (-44%) compared to IN. cRG-I could thus result in overall more robust beneficial effects, while also being better tolerated. Moreover, owing to its remarkable homogenization effect on microbial composition and metabolite production, cRG-I could lead to more predictable outcomes compared to substrates that are less specific or overly specific.
摘要：
人类肠道菌群的特点是人际差异大，这不仅与健康和疾病相关，而且决定了营养干预的结果。随着人们对开发靶向肠道微生物群调节剂的兴趣日益浓厚，将胡萝卜衍生的鼠李糖半乳糖醛酸I（cRG-I）的选择性与证明较低（菊粉，IN)和高选择性(黄原胶，XA),在1.5g/d的人类等效剂量（HED）。体外SIFR®技术的高通量，验证以生成临床发现的预测性见解，允许包括24名成年人。在体外肠道微生物群建模的背景下，这种前所未有的大量样品允许覆盖临床相关的肠道微生物群组成和功能的人际差异。一个关键发现是cRG-I补充剂（已经在0.3g/d的HED下）降低了人际组成差异，这是由于在成年人中始终存在的分类群的选择性刺激，包括与Dorei/vulgatus和长双歧杆菌相关的OTU(疑似梯形物种)，拟杆菌，青春双歧杆菌和产生丁酸的分类群，例如Blautiasp。,hallii厌氧丁酸，和prausnitzii粪杆菌.相比之下,IN和XA治疗都增加了人际组成差异。对于IN,这是因为其特异性低。对于XA，正是XA发酵的极高选择性导致了15个反应者和9个无反应者之间的巨大差异，由存在/不存在高度特异性的XA发酵类群引起。虽然所有测试化合物都显着增强乙酸，丙酸盐,丁酸盐,和天然气生产，cRG-I导致明显更高的乙酸（+40%），丙酸盐（+22%），然而，与国内相比，天然气产量较低（-44%）。因此，cRG-I可以产生总体上更稳健的有益效果，同时也有更好的耐受性。此外，由于其对微生物组成和代谢产物产生的显着均质化作用，与特异性较低或过度特异性的底物相比,cRG-I可导致更可预测的结果。
