Table_6_Administration of Bifidobacterium animalis subsp. lactis strain BB-12® in healthy children: characterization, functional composition, and metabolism of the gut microbiome.DOCX

IntroductionThe consumption of probiotics may influence children’s gut microbiome and metabolome, which may reflect shifts in gut microbial diversity composition and metabolism. These potential changes might have a beneficial impact on health. However, there is a lack of evidence investigating the effect of probiotics on the gut microbiome and metabolome of children. We aimed to examine the potential impact of a two (Streptococcus thermophilus and Lactobacillus delbrueckii; S2) vs. three (S2 + Bifidobacterium animalis subsp. lactis strain BB-12) strain-supplemented yogurt.
MethodsIncluded in this study were 59 participants, aged one to five years old, recruited to phase I of a double-blinded, randomized controlled trial. Fecal samples were collected at baseline, after the intervention, and at twenty days post-intervention discontinuation, and untargeted metabolomics and shotgun metagenomics were performed.
ResultsShotgun metagenomics and metabolomic analyses showed no global changes in either intervention group’s gut microbiome alpha or beta diversity indices, except for a lower microbial diversity in the S2 + BB12 group at Day 30. The relative abundance of the two and three intervention bacteria increased in the S2 and S2 + BB12 groups, respectively, from Day 0 to Day 10. In the S2 + BB12 group, the abundance of several fecal metabolites increased at Day 10, including alanine, glycine, lysine, phenylalanine, serine, and valine. These fecal metabolite changes did not occur in the S2 group.
DiscussionIn conclusion, there were were no significant differences in the global metagenomic or metabolomic profiles between healthy children receiving two (S2) vs. three (S2 + BB12) probiotic strains for 10 days. Nevertheless, we observed a significant increase (Day 0 to Day 10) in the relative abundance of the two and three probiotics administered in the S2 and S2 + BB12 groups, respectively, indicating the intervention had a measurable impact on the bacteria of interest in the gut microbiome. Future research using longer probiotic intervention durations and in children at risk for gastrointestinal disorders may elucidate if functional metabolite changes confer a protective gastrointestinal effect.

引言
益生菌摄入或可影响儿童肠道微生物组（gut microbiome）与代谢组（metabolome），该影响可反映肠道微生物多样性组成及代谢模式的变化。此类潜在改变或对健康产生有益效应。然而，目前尚缺乏探究益生菌对儿童肠道微生物组及代谢组影响的相关证据。本研究旨在对比分析两种益生菌酸奶（添加嗜热链球菌<Streptococcus thermophilus>与德氏乳杆菌<Lactobacillus delbrueckii>，记为S2组）与三种益生菌酸奶（S2联合动物双歧杆菌乳亚种BB-12<Bifidobacterium animalis subsp. lactis strain BB-12>，记为S2+BB12组）的潜在干预效果。

方法
本研究纳入59名1至5岁的受试者，均招募至一项双盲随机对照试验的I期阶段。分别于基线期、干预结束时及干预终止后20天采集粪便样本，并开展非靶向代谢组学（untargeted metabolomics）与鸟枪法宏基因组学（shotgun metagenomics）检测。

结果
鸟枪法宏基因组学与代谢组学分析显示，两组干预组的肠道微生物组α多样性与β多样性指数均未出现整体变化，仅S2+BB12组在第30天时的微生物多样性水平更低。从第0天至第10天，S2组与S2+BB12组的干预菌株相对丰度分别显著升高。在S2+BB12组中，第10天时粪便内多种代谢物丰度出现上升，包括丙氨酸、甘氨酸、赖氨酸、苯丙氨酸、丝氨酸及缬氨酸；而S2组未出现此类粪便代谢物变化。

讨论
综上，连续10天摄入两种（S2组）或三种（S2+BB12组）益生菌的健康儿童，其整体宏基因组与代谢组学特征未出现显著差异。但本研究观察到，从第0天至第10天，S2组与S2+BB12组的施用益生菌相对丰度分别显著升高，表明该干预对肠道微生物组中的目标菌株具有可检测的影响。未来可通过延长益生菌干预时长，以及纳入存在胃肠道疾病风险的儿童开展研究，以明确此类功能性代谢物变化是否可产生胃肠道保护效应。