Safety and functional enrichment of gut microbiome in healthy subjects consuming a multi-strain fermented milk product: a randomised controlled trial.

Safety and functional enrichment of gut microbiome in healthy subjects consuming a multi-strain fermented milk product: a randomised controlled trial.
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DOI:
10.1038/s41598-020-72161-w
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发表时间:
2020-09-29
期刊:
影响因子:
4.6
通讯作者:
Derrien M
Derrien M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Alvarez AS;Tap J;Chambaud I;Cools-Portier S;Quinquis L;Bourlioux P;Marteau P;Guillemard E;Schrezenmeir J;Derrien M

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许多临床研究已经评估了益生菌的效果,但只有少数研究评估了它们对肠道微生物群和宿主的剂量影响。我们进行了一项随机、双盲、对照干预临床试验,以评估96名健康成年人每天摄入两种剂量(1瓶或3瓶/天)的发酵乳制品(试验)的安全性(主要终点)和肠道微生物群反应(次要终点)。试验产品是一种多菌株发酵乳制品,将酸奶菌株和益生菌候选菌株副干酪乳杆菌亚种(Lactobacillus paracasei subsp.副干酪CNCM I-1518和CNCM I-3689和鼠李糖乳杆菌CNCM I-3690。我们根据以下参数评估了试验产品的安全性:不良事件、生命体征、血液学和代谢特征、肝、肾或甲状腺功能、炎症标志物、排便习惯和消化道症状。我们通过16 S rRNA基因测序和鸟枪宏基因组学的功能贡献,探索了纵向肠道微生物群对产品消费和剂量的反应。安全性结果显示,在4周期间每天摄入两种剂量时,无论评估的参数如何,供试品和对照品之间均无任何显著差异。益生菌候选菌株仅在食用期间检测到,并且在每天食用3瓶产品的受试者中,三种菌株的水平显著更高。通过α和β-多样性评估的肠道微生物群的整体结构没有因食用该产品四周而改变。具有随机效应的零膨胀β回归模型(ZIBR)鉴定了与对照相比对试验产品消耗剂量具有差异反应的几个细菌属。鸟枪宏基因组学分析揭示了益生菌候选物对肠道微生物组的功能贡献。
Many clinical studies have evaluated the effect of probiotics, but only a few have assessed their dose effects on gut microbiota and host. We conducted a randomized, double-blind, controlled intervention clinical trial to assess the safety (primary endpoint) of and gut microbiota response (secondary endpoint) to the daily ingestion for 4 weeks of two doses (1 or 3 bottles/day) of a fermented milk product (Test) in 96 healthy adults. The Test product is a multi-strain fermented milk product, combining yogurt strains and probiotic candidate strains Lactobacillus paracasei subsp. paracasei CNCM I-1518 and CNCM I-3689 and Lactobacillus rhamnosus CNCM I-3690. We assessed the safety of the Test product on the following parameters: adverse events, vital signs, hematological and metabolic profile, hepatic, kidney or thyroid function, inflammatory markers, bowel habits and digestive symptoms. We explored the longitudinal gut microbiota response to product consumption and dose, by 16S rRNA gene sequencing and functional contribution by shotgun metagenomics. Safety results did not show any significant difference between the Test and Control products whatever the parameters assessed, at the two doses ingested daily over a 4-week-period. Probiotic candidate strains were detected only during consumption period, and at a significantly higher level for the three strains in subjects who consumed 3 products bottles/day. The global structure of the gut microbiota as assessed by alpha and beta-diversity, was not altered by consumption of the product for four weeks. A zero-inflated beta regression model with random effects (ZIBR) identified a few bacterial genera with differential responses to test product consumption dose compared to control. Shotgun metagenomics analysis revealed a functional contribution to the gut microbiome of probiotic candidates.
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