Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, NE1 8ST, United Kingdom.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Alkek Center for Metagenomics and Microbiome Research, Houston, Texas, 77030, USA.
Microbiome. 2016 Dec 29;4(1):67. doi: 10.1186/s40168-016-0216-8.
The preterm microbiome is crucial to gut health and may contribute to necrotising enterocolitis (NEC), which represents the most significant pathology affecting preterm infants. From a cohort of 318 infants, <32 weeks gestation, we selected 7 infants who developed NEC (defined rigorously) and 28 matched controls. We performed detailed temporal bacterial (n = 641) and metabolomic (n = 75) profiling of the gut microbiome throughout the disease.
A core community of Klebsiella, Escherichia, Staphyloccocus, and Enterococcus was present in all samples. Gut microbiota profiles grouped into six distinct clusters, termed preterm gut community types (PGCTs). Each PGCT reflected dominance by the core operational taxonomic units (OTUs), except of PGCT 6, which had high diversity and was dominant in bifidobacteria. While PGCTs 1-5 were present in infants prior to NEC diagnosis, PGCT 6 was comprised exclusively of healthy samples. NEC infants had significantly more PGCT transitions prior to diagnosis. Metabolomic profiling identified significant pathways associated with NEC onset, with metabolites involved in linoleate metabolism significantly associated with NEC diagnosis. Notably, metabolites associated with NEC were the lowest in PGCT 6.
This is the first study to integrate sequence and metabolomic stool analysis in preterm neonates, demonstrating that NEC does not have a uniform microbial signature. However, a diverse gut microbiome with a high abundance of bifidobacteria may protect preterm infants from disease. These results may inform biomarker development and improve understanding of gut-mediated mechanisms of NEC.
早产儿的微生物组对肠道健康至关重要，可能会导致坏死性小肠结肠炎（NEC），这是影响早产儿的最重要的病理。我们从一个 318 名妊娠 <32 周的婴儿队列中，选择了 7 名发生了 NEC（严格定义）的婴儿和 28 名匹配的对照。我们对肠道微生物组进行了详细的时间细菌（n=641）和代谢组学（n=75）分析。
核心社区的克雷伯氏菌，大肠杆菌，葡萄球菌和肠球菌存在于所有样本中。肠道微生物群的轮廓分为六个不同的簇，称为早产肠道社区类型（PGCTs）。每个 PGCT 反映了核心操作分类单元（OTUs）的优势，除了 PGCT6，它具有高度的多样性，并且以双歧杆菌为主。虽然 PGCT1-5 存在于 NEC 诊断前的婴儿中，但 PGCT6 仅由健康样本组成。NEC 婴儿在诊断前有明显更多的 PGCT 转换。代谢组学分析确定了与 NEC 发病相关的显著途径，涉及亚油酸代谢的代谢物与 NEC 诊断显著相关。值得注意的是，与 NEC 相关的代谢物在 PGCT6 中最低。
这是第一项整合序列和代谢组学粪便分析的早产儿研究，表明 NEC 没有统一的微生物特征。然而，一个多样化的肠道微生物群，双歧杆菌丰度高，可能会保护早产儿免受疾病的侵害。这些结果可能为生物标志物的开发提供信息，并提高对肠道介导的 NEC 机制的理解。
