婴儿接受深度水解配方、氨基酸配方或母乳喂养至两个月时的粪便微生物群、pH 值和短链/支链脂肪酸。

BACKGROUND: 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). RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02500563 . Registered July 28, 2015.

背景：早期婴儿喂养完整或高度水解（EH）蛋白质或游离氨基酸（AA）可能会对肠道微生物群落组成和免疫反应产生不同的影响。这项多中心、双盲、对照、平行组、初步研究比较了健康足月婴儿的粪便微生物群，这些婴儿在出生后 1-7 天内接受了母亲的母乳（分配给人乳[HM]参考组）（n=25）或随机接受两种婴儿配方奶之一：基于 AA（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）并进行 16S rRNA 基因测序。分析α（香农、辛普森、Chao1）和β多样性（Bray Curtis）。分析相对分类群富集和倍数变化（Wilcoxon、DESeq2）。通过气相色谱法定量短/支链脂肪酸（S/BCFA）。分析平均 S/BCFA 和 pH（重复测量方差分析）。

结果：在基线时，所有组的α多样性测量值相似；然而，研究配方组在第 60 天时均显著高于 HM 组。第 60 天时还检测到β多样性的显著组间差异，并且与 HM 组相比，研究配方组的组成更为相似。双歧杆菌的相对丰度随时间增加，并在 HM 组第 60 天显著富集。相比之下，在第 60 天，研究配方组的厚壁菌门成员显著增加，同时 EHF 组中也有丁酸盐产生物种。AAF 组在第 30 天和第 60 天的粪便 pH 值显著升高。EHF 组的丁酸盐从基线到第 60 天显著增加，并且在第 60 天，EHF 组和研究配方组的丁酸盐均显著高于 HM 组。丙酸在第 30 天和第 60 天 EHF 和 AAF 组以及 AAF 组也显著高于 HM 组。通过第 60 天，AAF 和 EHF 组与 HM 组相比，总和个体 BCFA 均较高。

结论：与基于 AA 或高度水解蛋白的配方相比，接受母亲母乳的婴儿表现出早期新生儿微生物群、pH 值和微生物代谢产物的不同模式。在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产物。

临床试验注册：ClinicalTrials.gov 标识符：NCT02500563。2015 年 7 月 28 日注册。