Study of the composition and functional effects of gut microbiota in children infected with norovirus

Norovirus is the leading cause of sporadic cases and outbreaks of viral gastroenteritis. The gut microbiota plays important roles in energy and immune homeostasis of the gastrointestinal tract. The aim of this study was to investigate the composition and functional effects of gut microbiota in children infected with norovirus.Stool samples were collected from 31 children infected with norovirus and 25 healthy children. The gut microbiota was analyzed by 16S rRNA gene sequencing, followed by composition analysis, difference analysis, random forest model prediction analysis, correlation network analysis, functional and phenotype prediction analysis.Gut microbiota in children infected with norovirus was characterized by decreased species richness and diversity. Veillonella was dominant gut microbiota specie in norovirus infection. Rothia/Clostridium_sensu_stricto_1 and Romboutsia was respectively the most significantly increased and decreased gut microbiota specie in norovirus infection. Interestingly, Romboutsia, Turicibacter, Agathobacter, Eubacterium_hallii, Dorea, Blautia_obeum, Peptostreptococcaceae, Terrisporobacter and Odoribacter_splanchnicus were potential diagnostic biomarkers for norovirus infection. There was a positive interaction between Faecalibacterium, Blautia, Subdoligranulum, Eubacterium_hallii_group, Fusicatenibacter, Agathobacter, Roseburia and Dorea. Functionally, secondary metabolites biosynthesis, transport and catabolism, selenocysteine lyase and peroxiredoxin were the most significantly increased functional compositions of gut microbiota in norovirus infection. While, sn-glycerol-1-phosphate dehydrogenase and fermentation were the most significantly decreased functional compositions in norovirus infection group. Phenotype analysis showed that Contains_Mobile_Elements (contributed by Enterococcus_faecium) and Anaerobic (contributed by Bifidobacterium) was respectively the highest and lowest level of phenotypes in gut microbiota of norovirus infection.

诺如病毒（Norovirus）是引发散发性病毒性胃肠炎病例与暴发的首要病原体。肠道菌群（gut microbiota）在胃肠道的能量稳态与免疫稳态中发挥关键调控作用。本研究旨在探究诺如病毒感染儿童的肠道菌群组成特征及其功能效应。本研究收集了31名诺如病毒感染儿童与25名健康儿童的粪便样本，采用16S rRNA基因测序技术对肠道菌群进行检测分析，随后依次开展菌群组成分析、差异丰度分析、随机森林模型预测分析、关联网络分析以及功能与表型预测分析。诺如病毒感染儿童的肠道菌群以物种丰富度与多样性降低为典型特征。韦荣球菌属（Veillonella）为诺如病毒感染状态下的优势肠道菌群物种。罗氏菌属/梭菌簇XIIIa（Rothia/Clostridium_sensu_stricto_1）与罗姆布茨菌属（Romboutsia）分别为诺如病毒感染中丰度最显著升高与降低的肠道菌群物种。值得注意的是，罗姆布茨菌属（Romboutsia）、图里希杆菌属（Turicibacter）、阿加托杆菌属（Agathobacter）、霍氏真杆菌（Eubacterium_hallii）、多雷菌属（Dorea）、布劳特氏菌（Blautia_obeum）、消化链球菌科（Peptostreptococcaceae）、地孢杆菌属（Terrisporobacter）与内脏气味杆菌（Odoribacter_splanchnicus）可作为诺如病毒感染的潜在诊断生物标志物。粪杆菌属（Faecalibacterium）、布劳特氏菌属（Blautia）、亚多尔格拉努勒菌属（Subdoligranulum）、霍氏真杆菌群（Eubacterium_hallii_group）、链状梭菌属（Fusicatenibacter）、阿加托杆菌属（Agathobacter）、罗斯伯里氏菌属（Roseburia）与多雷菌属（Dorea）之间存在正向相互作用关系。功能层面分析显示，诺如病毒感染组肠道菌群的次级代谢产物生物合成、转运与分解代谢，硒半胱氨酸裂解酶以及过氧化物酶相关功能通路的丰度显著升高；而sn-甘油-1-磷酸脱氢酶（sn-glycerol-1-phosphate dehydrogenase）与发酵相关功能通路的丰度则在诺如病毒感染组中显著降低。表型分析结果表明，含移动元件（Contains_Mobile_Elements，由屎肠球菌Enterococcus_faecium贡献）与厌氧型（Anaerobic，由双歧杆菌属Bifidobacterium贡献）分别为诺如病毒感染儿童肠道菌群表型中丰度最高与最低的表型类型。