Genomics Research Center, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Microbiome. 2018 Oct 26;6(1):193. doi: 10.1186/s40168-018-0566-5.
Postnatal development of early life microbiota influences immunity, metabolism, neurodevelopment, and infant health. Microbiome development occurs at multiple body sites, with distinct community compositions and functions. Associations between microbiota at multiple sites represent an unexplored influence on the infant microbiome. Here, we examined co-occurrence patterns of gut and respiratory microbiota in pre- and full-term infants over the first year of life, a period critical to neonatal development.
Gut and respiratory microbiota collected as longitudinal rectal, throat, and nasal samples from 38 pre-term and 44 full-term infants were first clustered into community state types (CSTs) on the basis of their compositional profiles. Multiple methods were used to relate the occurrence of CSTs to temporal microbiota development and measures of infant maturity, including gestational age (GA) at birth, week of life (WOL), and post-menstrual age (PMA). Manifestation of CSTs followed one of three patterns with respect to infant maturity: (1) chronological, with CST occurrence frequency solely a function of post-natal age (WOL), (2) idiosyncratic to maturity at birth, with the interval of CST occurrence dependent on infant post-natal age but the frequency of occurrence dependent on GA at birth, and (3) convergent, in which CSTs appear first in infants of greater maturity at birth, with occurrence frequency in pre-terms converging after a post-natal interval proportional to pre-maturity. The composition of CSTs was highly dissimilar between different body sites, but the CST of any one body site was highly predictive of the CSTs at other body sites. There were significant associations between the abundance of individual taxa at each body site and the CSTs of the other body sites, which persisted after stringent control for the non-linear effects of infant maturity. Canonical correlations exist between the microbiota composition at each pair of body sites, with the strongest correlations between proximal locations.
These findings suggest that early microbiota is shaped by neonatal innate and adaptive developmental responses. Temporal progression of CST occurrence is influenced by infant maturity at birth and post-natal age. Significant associations of microbiota across body sites reveal distal connections and coordinated development of the infant microbial ecosystem.
生命早期微生物组在后生发展过程中影响免疫、代谢、神经发育和婴儿健康。微生物组在多个身体部位发育，具有不同的群落组成和功能。多个部位的微生物组之间的关联代表了对婴儿微生物组的一种未被探索的影响。在这里，我们研究了在生命的第一年中，早产儿和足月儿的肠道和呼吸道微生物组的共生模式，这是新生儿发育的关键时期。
从 38 名早产儿和 44 名足月儿的纵向直肠、喉咙和鼻腔样本中收集的肠道和呼吸道微生物组，首先根据其组成谱聚类为群落状态类型（CST）。使用多种方法将 CST 的出现与时间微生物组的发育和婴儿成熟度的测量相关联，包括出生时的胎龄（GA）、周龄（WOL）和月经后年龄（PMA）。CST 的表现与婴儿成熟度有以下三种模式之一：（1）随着时间的推移，CST 的出现频率仅与产后年龄（WOL）有关；（2）出生时的特殊性，CST 的出现间隔取决于婴儿的产后年龄，但出现频率取决于出生时的 GA；（3）趋同，在出生时成熟度较高的婴儿中首先出现 CST，早产儿的出现频率在产后间隔与早产程度成比例后收敛。不同身体部位的 CST 组成高度不同，但任何一个身体部位的 CST 都高度预测其他身体部位的 CST。每个身体部位的 CST 与其他身体部位的个体分类群的丰度存在显著关联，即使在严格控制婴儿成熟度的非线性效应后，这种关联仍然存在。每个身体部位的微生物组成之间存在典型相关性，与近端位置的相关性最强。
这些发现表明，早期微生物组是由新生儿先天和适应性发育反应塑造的。CST 出现的时间进程受出生时婴儿成熟度和产后年龄的影响。身体部位之间微生物组的显著关联揭示了远端连接和婴儿微生物生态系统的协调发展。
