Linking Human Milk Oligosaccharides, Infant Fecal Community Types, and Later Risk To Require Antibiotics
Linking Human Milk Oligosaccharides, Infant Fecal Community Types, and Later Risk To Require Antibiotics
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DOI：
10.1128/mbio.03196-19
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发表时间：
2020-03-01
期刊：
影响因子：
6.4
通讯作者：
Sprenger, Norbert
中科院分区：
文献类型：
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作者：
Berger, Bernard;Porta, Nadine;Sprenger, Norbert
人乳低聚糖（HMO）可以通过塑造早期肠道微生物群的发育为婴儿提供健康益处。在一项随机双盲对照多中心临床试验中，健康足月婴儿从入组（0至14天）至6个月接受婴儿配方奶粉（对照）或含两种HMO（2 '岩藻糖基乳糖和乳糖-N-新四糖;试验）的相同配方奶粉。然后，所有婴儿在12个月大之前接受相同的不含HMO的后续配方奶粉。母乳喂养的婴儿（BF）作为参照组。通过16 S rRNA基因测序分析，3个月和12个月的粪便微生物群聚类为7种粪便群落类型（FCT），总微生物丰度存在显著差异。四次12个月FCT中的三次可能是成人肠型的前体。在3个月时，通过微生物群α（组内）和β（组间）多样性分析和FCT分布，试验组（n = 58）中的微生物群组成似乎比对照组（n = 63）更接近BF（n = 35）。虽然双歧杆菌科在两个FCT中占主导地位，但其丰度在一个FCT中（双歧杆菌科的FCT BiH高丰度）明显高于另一个（双歧杆菌科的FCT Bi）。补充HMO增加了患有FCT BiH（主要在BF中）的婴儿数量，而FCT Bi（主要在对照中）则减少。我们探讨了FCT与报告的发病率和药物使用长达12个月的相关性。在第一年，使用配方奶粉喂养的婴儿在3个月时使用FCT BiH的可能性明显低于使用FCT Bi的婴儿。因此，此前报道的使用HMO的感染相关药物的比例较低可能与肠道微生物群类型有关。重要性母乳是新生儿唯一推荐的营养品，含有多种低聚糖的最大成分之一，被称为母乳低聚糖（HMO）。临床前和临床关联研究表明，HMO具有多种生理功能，主要通过建立肠道微生物组来介导。直到最近，HMO还无法调查其在随机对照干预试验中的作用。据我们所知，这是关于2种HMO对新生儿建立微生物群的影响的第一份报告。我们提供了与母乳喂养的参考婴儿的微生物群相比，在喂养含有2种HMO的配方奶粉时观察到的微生物群变化的详细描述。然后，我们将微生物群与处方抗生素使用评估的长期健康相关联。
Human milk oligosaccharides (HMOs) may provide health benefits to infants partly by shaping the development of the early-life intestinal microbiota. In a randomized double-blinded controlled multicentric clinical trial, healthy term infants received either infant formula (control) or the same formula with two HMOs (2'fucosyllactose and lacto-N-neotetraose; test) from enrollment (0 to 14 days) to 6 months. Then, all infants received the same follow-up formula without HMOs until 12 months of age. Breastfed infants (BF) served as a reference group. Stool microbiota at 3 and 12 months, analyzed by 16S rRNA gene sequencing, clustered into seven fecal community types (FCTs) with marked differences in total microbial abundances. Three of the four 12-month FCTs were likely precursors of the adult enterotypes. At 3 months, microbiota composition in the test group (n = 58) appeared closer to that of BF (n = 35) than control (n = 63) by microbiota alpha (within group) and beta (between groups) diversity analyses and distribution of FCTs. While bifidobacteriaceae dominated two FCTs, its abundance was significantly higher in one (FCT BiH for Bifidobacteriaceae at high abundance) than in the other (FCT Bi for Bifidobacteriaceae). HMO supplementation increased the number of infants with FCT BiH (predominant in BF) at the expense of FCT Bi (predominant in control). We explored the association of the FCTs with reported morbidities and medication use up to 12 months. Formula-fed infants with FCT BiH at 3 months were significantly less likely to require antibiotics during the first year than those with FCT Bi. Previously reported lower rates of infection-related medication use with HMOs may therefore be linked to gut microbiota community types.IMPORTANCE Human milk is the sole and recommended nutrition for the newborn infant and contains one of the largest constituents of diverse oligosaccharides, dubbed human milk oligosaccharides (HMOs). Preclinical and clinical association studies indicate that HMOs have multiple physiological functions largely mediated through the establishment of the gut microbiome. Until recently, HMOs were not available to investigate their role in randomized controlled intervention trials. To our knowledge, this is the first report on the effects of 2 HMOs on establishing microbiota in newborn infants. We provide a detailed description of the microbiota changes observed upon feeding a formula with 2 HMOs in comparison to breastfed reference infants' microbiota. Then, we associate the microbiota to long-term health as assessed by prescribed antibiotic use.