Mapping the early life gut microbiome in neonates with critical congenital heart disease: multiomics insights and implications for host metabolic and immunological health.
Mapping the early life gut microbiome in neonates with critical congenital heart disease: multiomics insights and implications for host metabolic and immunological health.
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DOI：
10.1186/s40168-022-01437-2
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发表时间：
2022-12-30
期刊：
影响因子：
15.5
通讯作者：
中科院分区：
文献类型：
--
作者：
早期肠道微生物群在维持宿主代谢和免疫动态平衡方面起着至关重要的作用。尽管患有严重先天性心脏病(CCHD)的新生儿面临营养不良和免疫失衡的巨大风险，但微生物与CCHD病理生理学的联系仍然知之甚少。在这项研究中，我们旨在研究CCHD新生儿肠道微生物群与代谢特征的关系。此外，我们还探讨了宿主-微生物相互作用在CCHD中的临床意义。对45例CCHD新生儿和50例健康对照的粪便样本进行了深度元基因组测序和代谢组学分析。从微生物丰度、功能和遗传变异三个维度对肠道微生物群特征进行了研究。对肠道病毒进行了深入的分析，以阐明肠道病毒和细菌群落之间的生态相互作用。用综合关联分析确定多水平微生物特征与粪便代谢物之间的相关性。最后，我们进行了亚组分析，以检查肠道微生物区系和代谢物之间的相互作用是否可以介导炎性反应和不良的手术预后。CCHD患儿肠道微生物区系失调，表现为双歧杆菌枯竭、肠球菌过度生长，与代谢紊乱密切相关。双歧杆菌和肠球菌的遗传变异协调了CCHD的代谢扰动。以沙门氏病毒科为代表的温带核心病毒体被证实通过改变微生物适应来影响肠道细菌组成。亚组分析显示肠球菌的过度生长与全身炎症和手术预后不良有关。中介分析表明，肠球菌的过度生长可介导CCHD的肠道屏障损伤和炎症反应。我们首次证明，与代谢紊乱相关的肠道微生物群异常与新生儿CCHD的免疫失衡和不良临床结局有关。我们的数据支持在CCHD中重建最优肠道微生物组在维持宿主代谢和免疫平衡方面的重要性。视频摘要在线版本包含可在10.1186/s40168022-01437-2上查阅的补充材料。
The early life gut microbiome is crucial in maintaining host metabolic and immune homeostasis. Though neonates with critical congenital heart disease (CCHD) are at substantial risks of malnutrition and immune imbalance, the microbial links to CCHD pathophysiology remain poorly understood. In this study, we aimed to investigate the gut microbiome in neonates with CCHD in association with metabolomic traits. Moreover, we explored the clinical implications of the host-microbe interactions in CCHD. Deep metagenomic sequencing and metabolomic profiling of paired fecal samples from 45 neonates with CCHD and 50 healthy controls were performed. The characteristics of gut microbiome were investigated in three dimensions (microbial abundance, functionality, and genetic variation). An in-depth analysis of gut virome was conducted to elucidate the ecological interaction between gut viral and bacterial communities. Correlations between multilevel microbial features and fecal metabolites were determined using integrated association analysis. Finally, we conducted a subgroup analysis to examine whether the interactions between gut microbiota and metabolites could mediate inflammatory responses and poor surgical prognosis. Gut microbiota dysbiosis was observed in neonates with CCHD, characterized by the depletion of Bifidobacterium and overgrowth of Enterococcus, which was highly correlated with metabolomic perturbations. Genetic variations of Bifidobacterium and Enterococcus orchestrate the metabolomic perturbations in CCHD. A temperate core virome represented by Siphoviridae was identified to be implicated in shaping the gut bacterial composition by modifying microbial adaptation. The overgrowth of Enterococcus was correlated with systemic inflammation and poor surgical prognosis in subgroup analysis. Mediation analysis indicated that the overgrowth of Enterococcus could mediate gut barrier impairment and inflammatory responses in CCHD. We demonstrate for the first time that an aberrant gut microbiome associated with metabolomic perturbations is implicated in immune imbalance and adverse clinical outcomes in neonates with CCHD. Our data support the importance of reconstituting optimal gut microbiome in maintaining host metabolic and immunological homeostasis in CCHD. Video Abstract The online version contains supplementary material available at 10.1186/s40168-022-01437-2.
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DOI：
10.1093/bioinformatics/bts565
发表时间：
2012-12-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Fu L;Niu B;Zhu Z;Wu S;Li W
通讯作者：
Li W
影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
11.4
作者：
Daiber A;Hahad O;Andreadou I;Steven S;Daub S;Münzel T
通讯作者：
Münzel T
影响因子：
64.5
作者：
Camarillo-Guerrero LF;Almeida A;Rangel-Pineros G;Finn RD;Lawley TD
通讯作者：
Lawley TD
影响因子：
4.4
作者：
Cheng, Chien-Hsiung;Lin, Ping-Ting;Huang, Yi-Chia
通讯作者：
Huang, Yi-Chia