Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles.
Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles.
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DOI：
10.1128/mbio.00441-18
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发表时间：
2018-04-10
期刊：
影响因子：
6.4
通讯作者：
Banfield JF
中科院分区：
文献类型：
--
作者：
Brown CT;Xiong W;Olm MR;Thomas BC;Baker R;Firek B;Morowitz MJ;Hettich RL;Banfield JF
在生命的最初几周，肠道微生物的定植会影响人体免疫系统的成熟和其他发育过程。在早产儿中，异常定植与坏死性小肠结肠炎（NEC）的发病有关，NEC是一种危及生命的肠道疾病。为了研究早产儿肠道定植过程，对新生儿重症监护病房35名早产儿（其中14名发生NEC）出生后3个月内收集的343份粪便样本进行了基因组解析宏基因组学研究，并对87份样本进行了元蛋白质组学测量。微生物群落组成和蛋白质组学特征在一周的时间尺度上保持相对稳定，但蛋白质组学变化较大。虽然遗传上相似的生物定植在许多婴儿身上，但大多数婴儿的定植是不同的菌株，这些菌株具有代谢谱，可以用宏蛋白质组学来区分。微生物组组成与婴儿、抗生素给药和NEC诊断相关。群落可分为7种主要类型，并且在婴儿体内可多次转换。有趣的是，在随后的时间点上，从同一婴儿中抽样的一些社区与其他婴儿的社区聚集在一起。在某些情况下，开关先于NEC发病；然而，没有物种或群落类型可以解释大多数婴儿的NEC。除了蛋白质丰度与生物复制率相关外，我们还发现生物蛋白质组与整体群落组成相关。因此，这项基因组解析蛋白质组学研究表明，个体生物对微生物组发育的贡献取决于微生物群落背景。人类在出生时就被微生物定植，这一过程对健康和发育很重要。然而，在定植期间发生的精细尺度微生物动力学仍有待了解。我们对健康和患病早产儿出生后头3个月的微生物群落组成、复制率和蛋白质组进行了基因组解析研究。婴儿被发现被相似的微生物定植，但每个都经历了不同的定植轨迹。有趣的是，在不同婴儿体内定植的相关微生物被发现具有不同的蛋白质组，这表明微生物组的功能不仅由存在的微生物驱动，而且在很大程度上取决于微生物对婴儿肠道独特生理条件的反应。
During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context. Humans are colonized by microbes at birth, a process that is important to health and development. However, much remains to be known about the fine-scale microbial dynamics that occur during the colonization period. We conducted a genome-resolved study of microbial community composition, replication rates, and proteomes during the first 3 months of life of both healthy and sick premature infants. Infants were found to be colonized by similar microbes, but each underwent a distinct colonization trajectory. Interestingly, related microbes colonizing different infants were found to have distinct proteomes, indicating that microbiome function is not only driven by which organisms are present, but also largely depends on microbial responses to the unique set of physiological conditions in the infant gut.