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文章Dynamics of Infant Gut Microbiota...的内容解读
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文章：Dynamics of Infant Gut Microbiota Are Influenced by Delivery Modeand Gestational Duration and Are Associated with Subsequent Adiposity
杂志：MBio
文中一些观点的考虑：
1）At birth, human infants start accumulating intestinal microbiota until a relatively stable state is reached. 什么叫稳定状态？如何界定稳定？稳定状态时人体菌群组成和含量是怎样的分布特征？这种稳定状态不同人之间是相似的还是存在较大个体差异？不同民族、不同性别、不同区域、不同国度，稳定状态是相似的吗？
2）The rate and trajectory of acquisition of a gut microbiota is hypothesized to have a considerable impact on later health outcomes. 具体是什么样的影响？健康的菌群组成与含量是怎样的？
研究内容：Here we have studied gut microbiota acquisition in 75 infants participating in the Growing Up in Singapore Toward Healthy Outcomes (GUSTO) birth cohort (21). The microbial content of longitudinal fecal samples during the first 6 months of life was profiled by 16S rRNA sequencing, and we investigated the effect of environmental factors, including the delivery mode and durationof gestation, on the trajectories of microbial development, along with the associative relationships with later adiposity. 75个新生儿样本，跟踪3天、3周、3个月、6个月的肠道菌群变化，通过16s 的v456区，探索分娩方式、孕周与肠道菌群的关系。
研究结论：
1）菌落种类较少，组成单一，The microbiotas were simple, with three of the four abundant phyla (Actinobacteria, Proteobacteria, Firmicutes and Bacteroidetes) represented by only one detectable genus and few operational taxonomic units(OTUs);
2）个体差异大，There was substantial interindividual variation in the microbiota composition of infant feces.
3）随着孩子的成长，双歧杆菌逐渐成为肠道内的优势菌，Day 3 neonate microbiotas were dominated by Klebsiella OTU2 and Escherichia OTU3, which belong to the family Enterobacteriaceae (of the phylum Proteobacteria), and these levels decreased over time with a commensurate increase in the levels of members of the genus Bifidobacterium (which was the only genus in the phylum Actinobacteria detected) represented by one major OTU.
4）The phylum Firmicutes retained similar abundance levels across time but with changing constituent genera，The genus Bacteroides (the only representative of the phylum Bacteroidetes detected) was detected in only a subset of the infants.
5）利用UPGMA计算euclidean distance进行聚类， Both taxa and samples are clustered by UPGMA with euclidean distance. 发现所有样品主要聚成3个类，如下图
Most of the day 3 samples were in cluster 2, which was characterized by high levels of Enterobacteriaceae family members, especially Klebsiella OTU2; in contrast, the majority of the month 6 samples belonged to the biggest cluster, 3, which was characterized by high Bifidobacterium OTU1 and Collinsella levels. Cluster3中主要是双歧杆菌
Most subjects progressed from cluster 2 to cluster 3 throughout the 6-month time frame. at day 3, 19 of the73 samples were in cluster 3, demonstrating interindividual variability in progression over time. Once a sample from an individual was classified in cluster 3, later samples from the same individual tended also to be classified within cluster 3. Finally, there was a minority of samples within cluster 1. 绝大部分样本在6个月时，基本上处于cluster3，对于每个孩子在不同时间所处的cluster，如下图所示
对比剖腹产和自然分娩，发现Infants delivered by caesarean section reached (and remained in) cluster 3 later than infants delivered vaginally. Of the 17 individuals who reached a cluster 3 microbiota at day 3, just 1(6%) was delivered by caesarean section, while 16 had vaginal deliveries; for those reaching cluster 3 at week 3, the month 3 and 6 comparable figures for the proportions delivered by caesarean section were 25% (6 of 24), 33% (5 of 15), and 40% (2 of 5),respectively. 具体如下图所示
剖腹产和自然分娩在双歧杆菌和克雷白氏杆菌的含量上存在显著差异. This is consistent with univariate analysis showing significantly lower levels (P ＝0.042) of Bifidobacterium OTU1 detected in babies delivered by caesarean section than inbabies delivered vaginally at day 3 and significantly higher levels (P＝5.8E8) of Klebsiella OTU2. 如下图所示
Babies who reached cluster 3 later tended to be born earlier，The difference in the mean duration of gestation between infants who reached cluster 3 on day 3 and those who did so by month 6 was only 1 week, suggesting thata shorter gestational duration is associated with a lag in microbial acquisition. 孕周时间短易促使孩子较晚达到cluster 3. 具体如下图所示
孕周的不同，菌群含量存在不同. This observation is consistent with the within-timepoint analysis showing that babies born after a shorter duration of gestation tend to have higher Streptococcus levels at week 3.
There was also an association between reaching cluster 3 later and lower subscapular skinfold thickness at 18 months. subscapular skinfold thickness是adiposity的一个评价指标。Interestingly, Streptococcus levels at month 6 wereassociated with the change in subscapular skinfold thickness between 0 and 18 months.
这篇文章比较有意思的是找到了3个cluster，这个未来建立健康标准时可以参考。
75个样本，跟踪了3天、3周、3个月、6个月，未来可以考虑时间点更加细化一些，样本量增加一些。
孕周对菌群的影响，鉴于差1周就有明显区别，未来可以在扩大样本量的基础上，以天作为记录去分析。
双歧杆菌作为cluster 3的优势菌，或许可以借鉴痛风菌群的模型去建立1个指标。
https://blog.sciencenet.cn/blog-306699-987498.html
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