人源诺如病毒感染引起的急性胃肠炎儿童肠道微生物群组成差异分析

doi:10.19871/j.cnki.xfcrbzz.2025.05.008

摘要/Abstract

摘要： 目的探讨症状性人源诺如病毒（human norovirus,HNoV）感染儿童肠道微生物群特征并进行功能分析。方法纳入2024年7月至2024年11月期间因HNoV感染引起急性胃肠炎在重庆医科大学附属大足医院儿科就诊的25例学龄前儿童作为HNoV组,另外按照倾向评分匹配原则纳入同期25例HNoV GII基因扩增阴性的健康儿童作为对照组。收集两组儿童粪便样本并分析肠道微生物群特征。通过生物信息学分析评估肠道微生物α多样性、β多样性、不同丰度的分类群和微生物功能。结果与对照组相比,HNoV组肠道微生物群富含厚壁菌门（62.25%比57.24%）,而放线菌门（1.57%比3.02%）和拟杆菌门（0.22%比1.14%）占比相对降低,厚壁菌门/拟杆菌门比值升高（17.21%比11.20%比17.21%,P=0.003）。同样,两组样本在科（Family）和属（Genus）水平上都发现了显著的微生物差异,韦荣氏球菌属（P=0.006）、巨单胞菌属（P=0.017）、肠球菌属（P=0.020）和梭状芽孢杆菌属（P=0.036）在HNoV组中的丰度高于对照组。这些肠道微生物群的差异伴随着参与次生代谢物生物合成、转运和分解代谢的基因差异,包括硝酸还原酶功能增加和烷基氢过氧化物还原酶亚基C丰度升高。结论 HNoV组肠道微生物群丰度和多样性存在显著差异,并且肠道微生物群组成和功能的显著失调。

关键词: 人源人类诺如病毒, 肠道微生物群, 16S rRNA扩增子焦磷酸测序, 功能预测

Abstract: Objective To investigate the characteristics of gut microbiota in children with symptomatic human norovirus (HNoV) infection and to perform functional analysis. Method Twenty-five preschool children who received treatment for acute gastroenteritis caused by HNoV infection in the Pediatrics Department of Dazu Hospital affiliated to Chongqing Medical University from July 2024 to November 2024 were included as the HNoV group. In addition, 25 healthy children who tested negative for HNoV GII gene amplification were included as the control group according to the propensity score matching principle. Fecal samples from both groups were collected to analyze gut microbiota characteristics. Evaluate alpha-diversity, beta-diversity, taxonomic groups with different abundance, and microbial functions through bioinformatics analysis. Result Compared with the control group, the gut microbiota of the HNoV group was enriched in Firmicutes (62.25% vs 57.24%), while the proportions of Actinobacteria (1.57% vs 3.02%) and Bacteroidetes (0.22% vs 1.14%) were relatively reduced, and leading to an increased Firmicutes/Bacteroidetes ratio(11.20% vs 17.21%, P=0.003). Similarly, significant microbial differences were observed at both the family and genus levels between the two groups. The abundances of Vibrio (P=0.006), Pseudomonas (P=0.017), Enterococcus (P=0.020), and Clostridium (P=0.036) in the HNoV group were higher than those in the control group. The differences in these microorganisms were accompanied by genetic variations involved in the biosynthesis, transport, and catabolism of secondary metabolites, particularly an increased function of nitrate reductase and an elevated abundance of alkyl hydroperoxide reductase subunit C, which may contribute to greater susceptibility to HNoV. Conclusion HNoV infection leads to significant reduction in gut microbiota abundance and diversity and significant dysregulation of gut microbiota composition and function in children.

Key words: Human norovirus, Gut microbiota, 16S rRNA amplicon pyrophosphate sequencing, Function prediction

中图分类号:

R512.5

王廷婷, 雷芳, 杨阳, 陈岑, 周延. 人源诺如病毒感染引起的急性胃肠炎儿童肠道微生物群组成差异分析[J]. 新发传染病电子杂志, 2025, 10(5): 41-46.

Wang Tingting, Lei Fang, Yang Yang, Chen Cen, Zhou Yan. Differences in gut microbiota composition in children with acute gastroenteritis due to human norovirus[J]. Electronic Journal of Emerging Infectious Diseases, 2025, 10(5): 41-46.

参考文献

[1] SCHERER D, SCHÖNWEISS C, DE ROCHE M, et al. Norovirus - an update for practitioners[J]. Praxis (Bern 1994), 2025, 114(3):99-104.
[2] ZHU M, HUANG Z, LIU T, et al.Global burden and trends of norovirus-associated diseases from 1990 to 2021 an observational trend study[J]. Front Public Health, 2025, 12:1483149.
[3] CARLSON KB, DILLEY A, O'GRADY T, et al. A narrative review of norovirus epidemiology, biology, and challenges to vaccine development[J]. NPJ Vaccines, 2024, 9(1):94.
[4] 吉彦莉, 王永全, 崔海洋, 等. 一起由诺如病毒和肠道腺病毒混合感染引起的急性胃肠炎聚集性疫情的病原鉴定及进化分析[J]. 传染病信息, 2023, 36(2):124-127.
[5] HANSMAN GS, KHER G, SVIRINA AD, et al.Development of a broad-spectrum therapeutic Fc-nanobody for human noroviruses[J]. J Virol, 2024, 98(7):e0070724.
[6] 杜雪, 赵印震, 张怡青, 等. 基于生物信息学诺如病毒多表位抗原的构建及鉴定[J]. 中国免疫学杂志, 2024, 40(11):2391-2398.
[7] 姬莉莉, 高志勇,耿晓飞, 等. 2012—2023年北京市怀柔区哨点医院病毒性腹泻监测结果分析[J]. 中国病毒病杂志, 2025, 15(1):60-65.
[8] SONG J, ZHANG L, MOON S, et al. Norovirus co-opts NINJ1 for selective protein secretion[J]. Sci Adv, 2025, 11(9):eadu7985.
[9] MIRMAHDI RS, MONTAZERI N.Progress and challenges in thermal inactivation of norovirus in oysters[J]. Crit Rev Food Sci Nutr, 2025:1-14.
[10] 曾昭成, 苏泽红, 张小燕. 诺如病毒急性胃肠炎流行特征及病原学特征分析[J]. 中国社区医师, 2024, 40(6): 149-151.
[11] 张彦, 张丹, 苏文冕, 等. 诺如病毒急性胃肠炎流行特征及疫苗研究进展[J]. 中国病原生物学杂志, 2024, 19(9):1112-1114.
[12] TAO L, WANG X, YU Y, et al.Identifying SNP threshold from P2 sequences for investigating norovirus transmission[J]. Virus Res, 2024, 346:199408.
[13] HE T, DENG Y, ZHANG F, et al.Characteristics of Norovirus capsid protein-specific CD8(+) T-Cell responses in previously infected individuals[J]. Virulence, 2024, 15(1):2360133.
[14] 梁耀民, 陆胤波, 曹颖雯, 等. 诺如病毒和肠道菌群的互作关系及机制研究进展[J]. 病毒学报, 2021, 37(5):1215-1220.
[15] SANTISO-BELLÓN C, RANDAZZO W, CARMONA-VICENTE N,et al. Rhodococcus spp. interacts with human norovirus in clinical samples and impairs its replication on human intestinal enteroids[J]. Gut Microbes, 2025, 17(1):2469716.
[16] 祝阳露, 张倩, 李四菊, 等. 狄氏副拟杆菌胞外多糖粗提物的免疫调节活性[J]. 中山大学学报(自然科学版)(中英文), 2022, 61(6):44-50.
[17] WANG L, GUO G, XU Y, et al.The effect of fecal microbiota transplantation on antibiotic-associated diarrhea and its impact on gut microbiota[J]. BMC Microbiol, 2024, 24(1):160.
[18] TIAN X, LI S, WANG C, et al.Gut virome-wide association analysis identifies cross-population viral signatures for inflammatory bowel disease[J]. Microbiome, 2024, 12(1):130.
[19] 陈培, 舒杨, 李洪辉, 等. 基于“肠菌-免疫-关节”轴探讨肠道微生物对痛风性关节炎疼痛机制的影响[J]. 中国微生态学杂志, 2024, 36(11):1344-1349.
[20] GUO J, ZHAO X, HU J, et al.Tobacco Mosaic Virus with Peroxidase-Like Activity for Cancer Cell Detection through Colorimetric Assay[J]. Mol Pharm, 2018, 15(8):2946-2953.
[21] HUANG L, ZHANG X, MAO Z, et al.Ni-Pt nanozyme-mediated relaxation and colorimetric sensor for dual-modality detection of norovirus[J]. Sci Total Environ, 2024, 914:169738.
[22] PEIPER AM, MORALES APARICIO J, HU Z, et al. Metabolic immaturity and breastmilk bile acid metabolites are central determinants of heightened newborn vulnerability to norovirus diarrhea[J]. Cell Host Microbe, 2024, 32(9):1488-1501.e5.
[23] WANG Z, WEI X, PIAO L, et al.Gut microbiota dysbiosis and metabolic shifts in pediatric norovirus infection: a metagenomic study in Northeast China[J]. Front Cell Infect Microbiol, 2025, 15:160047.
24 参考文献
[1] SCHERER D, SCHÖNWEISS C, DE ROCHE M, et al. Norovirus - an update for practitioners[J]. Praxis (Bern 1994), 2025, 114(3):99-104.
[2] ZHU M, HUANG Z, LIU T, et al.Global burden and trends of norovirus-associated diseases from 1990 to 2021 an observational trend study[J]. Front Public Health, 2025, 12:1483149.
[3] CARLSON KB, DILLEY A, O'GRADY T, et al. A narrative review of norovirus epidemiology, biology, and challenges to vaccine development[J]. NPJ Vaccines, 2024, 9(1):94.
[4] 吉彦莉, 王永全, 崔海洋, 等. 一起由诺如病毒和肠道腺病毒混合感染引起的急性胃肠炎聚集性疫情的病原鉴定及进化分析[J]. 传染病信息, 2023, 36(2):124-127.
[5] HANSMAN GS, KHER G, SVIRINA AD, et al.Development of a broad-spectrum therapeutic Fc-nanobody for human noroviruses[J]. J Virol, 2024, 98(7):e0070724.
[6] 杜雪, 赵印震, 张怡青, 等. 基于生物信息学诺如病毒多表位抗原的构建及鉴定[J]. 中国免疫学杂志, 2024, 40(11):2391-2398.
[7] 姬莉莉, 高志勇,耿晓飞, 等. 2012—2023年北京市怀柔区哨点医院病毒性腹泻监测结果分析[J]. 中国病毒病杂志, 2025, 15(1):60-65.
[8] SONG J, ZHANG L, MOON S, et al. Norovirus co-opts NINJ1 for selective protein secretion[J]. Sci Adv, 2025, 11(9):eadu7985.
[9] MIRMAHDI RS, MONTAZERI N.Progress and challenges in thermal inactivation of norovirus in oysters[J]. Crit Rev Food Sci Nutr, 2025:1-14.
[10] 曾昭成, 苏泽红, 张小燕. 诺如病毒急性胃肠炎流行特征及病原学特征分析[J]. 中国社区医师, 2024, 40(6): 149-151.
[11] 张彦, 张丹, 苏文冕, 等. 诺如病毒急性胃肠炎流行特征及疫苗研究进展[J]. 中国病原生物学杂志, 2024, 19(9):1112-1114.
[12] TAO L, WANG X, YU Y, et al.Identifying SNP threshold from P2 sequences for investigating norovirus transmission[J]. Virus Res, 2024, 346:199408.
[13] HE T, DENG Y, ZHANG F, et al.Characteristics of Norovirus capsid protein-specific CD8(+) T-Cell responses in previously infected individuals[J]. Virulence, 2024, 15(1):2360133.
[14] 梁耀民, 陆胤波, 曹颖雯, 等. 诺如病毒和肠道菌群的互作关系及机制研究进展[J]. 病毒学报, 2021, 37(5):1215-1220.
[15] SANTISO-BELLÓN C, RANDAZZO W, CARMONA-VICENTE N,et al. Rhodococcus spp. interacts with human norovirus in clinical samples and impairs its replication on human intestinal enteroids[J]. Gut Microbes, 2025, 17(1):2469716.
[16] 祝阳露, 张倩, 李四菊, 等. 狄氏副拟杆菌胞外多糖粗提物的免疫调节活性[J]. 中山大学学报(自然科学版)(中英文), 2022, 61(6):44-50.
[17] WANG L, GUO G, XU Y, et al.The effect of fecal microbiota transplantation on antibiotic-associated diarrhea and its impact on gut microbiota[J]. BMC Microbiol, 2024, 24(1):160.
[18] TIAN X, LI S, WANG C, et al.Gut virome-wide association analysis identifies cross-population viral signatures for inflammatory bowel disease[J]. Microbiome, 2024, 12(1):130.
[19] 陈培, 舒杨, 李洪辉, 等. 基于“肠菌-免疫-关节”轴探讨肠道微生物对痛风性关节炎疼痛机制的影响[J]. 中国微生态学杂志, 2024, 36(11):1344-1349.
[20] GUO J, ZHAO X, HU J, et al.Tobacco Mosaic Virus with Peroxidase-Like Activity for Cancer Cell Detection through Colorimetric Assay[J]. Mol Pharm, 2018, 15(8):2946-2953.
[21] HUANG L, ZHANG X, MAO Z, et al.Ni-Pt nanozyme-mediated relaxation and colorimetric sensor for dual-modality detection of norovirus[J]. Sci Total Environ, 2024, 914:169738.
[22] PEIPER AM, MORALES APARICIO J, HU Z, et al. Metabolic immaturity and breastmilk bile acid metabolites are central determinants of heightened newborn vulnerability to norovirus diarrhea[J]. Cell Host Microbe, 2024, 32(9):1488-1501.e5.
[23] WANG Z, WEI X, PIAO L, et al.Gut microbiota dysbiosis and metabolic shifts in pediatric norovirus infection: a metagenomic study in Northeast China[J]. Front Cell Infect Microbiol, 2025, 15:160047.