基于PacBio SMRT测序技术评估妊娠期糖尿病人的肠道菌群

PacBio SMRT sequencing of the intestinal flora composition in patients with gestational diabetes mellitus

摘要:

[目的]肠道菌群是位于人体肠道内的微生物菌群，其组成与人类多种疾病相关。例如，已有研究表明肠道菌群的变化与妊娠期糖尿病（gestational diabetes mellitus，GDM）的发病密切相关。因此本研究基于PacBio SMRT测序技术评估及比较了不同民族（汉族和蒙古族）及是否患GDM的孕妇的肠道菌群。[方法]本研究利用PacBio SMRT测序技术对97例患有GDM及健康的汉族和蒙古族孕妇粪便样本进行了全长16S rRNA测序及分析。[结果]总体来说，处于相同孕期的4组孕妇肠道菌群的组成相似，不同核心菌群展现出不同强弱的相关性。本研究在种的水平上共鉴定到了44个种。在汉族人中，患有妊娠期糖尿病的孕妇肠道菌群中Akkermansia muciniphila菌的相对丰度要显著低于健康孕妇；而在蒙古族人中，健康孕妇与GDM孕妇间差异并不明显。在健康对照中发现汉族孕妇肠道菌群中Bacteroides uniformis菌的相对丰度显著高于蒙古族孕妇；但在患有GDM组中未找到不同民族分组间的差异。另外，功能预测结果发现四组样本菌群功能组成高度相似，大多数功能基因都与能量代谢有关。汉族GDM患者与健康对照组间没有发现显著差异，但在蒙古族GDM患者中发现无机离子运输等功能相对丰度显著高于与蒙古族正常孕妇。[结论]在相同的孕期，妊娠期孕妇的核心肠道菌群结构与功能是相对稳定的，而民族差异也不会对妊娠期菌群产生显著性影响。但在四组间可以检测到一些低丰度的差异菌群，如Akkermansia muciniphila，其丰度的变化可能导致了肠道中一些与肠道营养吸收等有关的代谢发生变化，而这些变化可能与妊娠期糖尿病的发生密切相关。本研究将有助于探究肠道菌群在GDM发病机制中的作用。

Abstract:

[Objective] The intestinal flora represents the microbial flora located in the human intestine, and its composition has been related to the occurrence of various diseases in humans. For example, the intestinal flora plays an important role in the pathogenesis of gestational diabetes mellitus (GDM). Therefore, in this study, we evaluated and compared the intestinal flora in pregnant women according to ethnicity (Mongolian or Han) and GDM status using PacBio SMRT sequencing. [Methods] Ninety-seven fecal samples from pregnant women with or without GDM and of Han or Mongolian ethnicity were subjected to full-length 16S rRNA sequencing using the PacBio SMRT system. [Results] Overall, the microbial flora compositions of the pregnant women were similar during the same pregnant stage, and various microbes exhibited different degrees of correlation with core flora levels. We identified 44 species at the species level. The relative abundance of Akkermansia muciniphila was significantly higher in the non-GDM pregnant women than in pregnant women with GDM in the Han population, while no differences were found in the Mongolian women with and without GDM. The relative abundance of Bacteroides uniformis in the intestinal flora of healthy Han pregnant women was significantly higher than that in healthy Mongolian pregnant women, while no differences were found in the GDM groups between ethnicities. Moreover, the functional prediction results showed that the functional composition of the four groups of flora was highly similar, and most of the functional genes were related to energy metabolism. There was no significant difference between the GDM patients and controls in the Han population, but the relative abundance of flora related to inorganic ion transport in Mongolian GDM patients was significantly higher than that of healthy Mongolian pregnant women. [Conclusion] The intestinal flora is generally relatively stable during the same pregnant stage, and ethnic differences do not have a significant impact on the flora during pregnancy. However, changes in some low-abundance organisms such as Akkermansia muciniphila may contribute to alterations in some metabolic activities of the intestinal flora, including those related to intestinal nutrient absorption, which could influence the development of GDM. The results of this study can help elucidate the role of intestinal flora in GDM pathogenesis.