Early infant feeding with intact or extensively hydrolyzed (EH) proteins or free amino acids (AA) may differentially affect intestinal microbiota composition and immune reactivity. This multicenter, double-blind, controlled, parallel-group, pilot study compared stool microbiota from Baseline (1–7 days of age) up to 60 days of age in healthy term infants who received mother’s own milk (assigned to human milk [HM] reference group) (n = 25) or were randomized to receive one of two infant formulas: AA-based (AAF; n = 25) or EH cow’s milk protein (EHF; n = 28). Stool samples were collected (Baseline, Day 30, Day 60) and 16S rRNA genes were sequenced. Alpha (Shannon, Simpson, Chao1) and beta diversity (Bray Curtis) were analyzed. Relative taxonomic enrichment and fold changes were analyzed (Wilcoxon, DESEq2). Short/branched chain fatty acids (S/BCFA) were quantified by gas chromatography. Mean S/BCFA and pH were analyzed (repeated measures ANOVA). At baseline, alpha diversity measures were similar among all groups; however, both study formula groups were significantly higher versus the HM group by Day 60. Significant group differences in beta diversity at Day 60 were also detected, and study formula groups were compositionally more similar compared to HM. The relative abundance of Bifidobacterium increased over time and was significantly enriched at Day 60 in the HM group. In contrast, a significant increase in members of Firmicutes for study formula groups were detected at Day 60 along with butyrate-producing species in the EHF group. Stool pH was significantly higher in the AAF group at Days 30 and 60. Butyrate increased significantly from Baseline to Day 60 in the EHF group and was significantly higher in study formula groups vs HM at Day 60. Propionate was also significantly higher for EHF and AAF at Day 30 and AAF at Day 60 vs HM. Total and individual BCFA were higher for AAF and EHF groups vs HM through Day 60. Distinct patterns of early neonatal microbiome, pH, and microbial metabolites were demonstrated for infants receiving mother’s own milk compared to AA-based or extensively hydrolyzed protein formula. Providing different sources of dietary protein early in life may influence gut microbiota and metabolites. ClinicalTrials.gov Identifier: NCT02500563 . Registered July 28, 2015.

中文翻译：

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接受深度水解配方奶粉、氨基酸配方奶粉或母乳的婴儿至两个月龄的粪便微生物组、pH 值和短/支链脂肪酸

早期婴儿喂养完整或深度水解 (EH) 蛋白质或游离氨基酸 (AA) 可能会对肠道微生物群组成和免疫反应性产生不同影响。这项多中心、双盲、对照、平行组试点研究比较了接受母乳（分配为母乳）的健康足月婴儿从基线（1-7 天龄）到 60 天龄的粪便微生物群] 参考组）（n = 25）或随机接受两种婴儿配方奶粉之一：AA 配方奶粉（AAF；n = 25）或 EH 牛奶蛋白（EHF；n = 28）。收集粪便样本（基线、第 30 天、第 60 天）并对 16S rRNA 基因进行测序。分析了 Alpha（Shannon、Simpson、Chao1）和 beta 多样性（Bray Curtis）。分析了相对分类富集和倍数变化（Wilcoxon，DESEq2）。通过气相色谱法对短/支链脂肪酸（S/BCFA）进行定量。分析平均 S/BCFA 和 pH（重复测量方差分析）。在基线时，所有组的阿尔法多样性测量值相似；然而，到第 60 天，两个研究配方奶粉组均显着高于 HM 组。第 60 天时，还检测到了 β 多样性的显着组间差异，并且与 HM 相比，研究配方奶粉组在成分上更加相似。双歧杆菌的相对丰度随着时间的推移而增加，并且在 HM 组中第 60 天显着富集。相比之下，在第 60 天时检测到研究配方组的厚壁菌门成员以及 EHF 组中产生丁酸盐的物种显着增加。在第 30 天和第 60 天，AAF 组的粪便 pH 值显着升高。在 EHF 组中，丁酸盐从基线到第 60 天显着增加，并且在第 60 天，研究配方组与 HM 组相比显着更高。EHF 和 AAF 的丙酸盐也显着更高第 30 天的 AAF 和第 60 天的 AAF 对比 HM。到第 60 天，AAF 和 EHF 组的总 BCFA 和个体 BCFA 均高于 HM 组。与 AA 或深度水解蛋白配方奶粉相比，接受母乳的婴儿的早期新生儿微生物组、pH 值和微生物代谢物具有不同的模式。生命早期提供不同来源的膳食蛋白质可能会影响肠道微生物群和代谢物。ClinicalTrials.gov 标识符：NCT02500563。2015年7月28日注册。