文章：Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls

杂志：Microbiome

时间：2017

研究目的：We aimed to explore relationships between gut microbiome and metabolome to determine key insights into LOS development, impact, and recovery.  

研究方案：we present comprehensive longitudinal gut microbiome data on 613 stool samples from LOS infants (n = 7) and well-matched non-diseased (no NEC or LOS) controls (n = 28). A subset of 63 stool samples from LOS infants (n = 4) and matched controls (n = 10) also underwent UPLC-MS.

研究结果：

   1）The pathogen identified by blood culture was one of the most abundant OTUs in the gut microbiota at diagnosis, with the corresponding genus from the gut microbiome the most abundant in four cases and second most abundant OTU in two cases. An exception was Staphylococcus epidermidis LOS in infant 251, which was the seventh most abundant genus at diagnosis.  血液中的病原菌，在肠道中是丰度较高的OTU，有1个样本较为特殊。具体结果如下图

   2）All samples grouped into six discrete clusters: dominance of Klebsiella (PGCT 1), dominance of both Klebsiella and Enterococcus (PGCT 2), dominance of Staphylococcus(PGCT 3), dominance of Enterococcus(PGCT 4), dominance of Escherichia (PGCT 5), and mixed population with high relative abundance of Bifidobacterium (PGCT 6). No PGCT was strongly associated with PreLOS samples when compared to all control samples, where as PGCT 2 and PGCT 6 were never found in any sample from LOS infants before diagnosis, Conversely PGCT 6, which represents a diverse community high in relative Bifidobacterium abundance, was present frequently throughout the control population from early to late samples. 菌群随时间的变化，control组富含较多以Bifidobacterium为主的PGCT6.

   3）代谢组在LOS阳性鉴定那天有明显差异，Fourteen stool metabolites were identified as significantly altered between LOS and control infants at diagnosis (TP3), with 7 metabolites (all increased incontrols) remaining significant following adjustment for 7 confounders.

总结：

      1）数据的分析下，抛弃了差异菌的分析，采用community type的策略，起到较好的效果；