Journal of Shandong University (Health Sciences) ›› 2026, Vol. 64 ›› Issue (5): 116-124.doi: 10.6040/j.issn.1671-7554.0.2025.0579

• Public Health and Preventive Medicine • Previous Articles    

Early childhood multi-niche viromes: unclassified phage diversity and host features

YANG Jing1,2,3, ZHANG Lei1,2,3   

  1. 1. Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. National Institute of Health and Medical Big Data, Jinan 250003, Shandong, China;
    3. Microbiome-X, Jinan 250012, Shandong, China
  • Online:2026-05-13 Published:2026-05-13

PDF (PC)

3

Abstract: Objective To construct a multi-niche viromic dataset in early childhood and analyze the structural characteristics and bacterial hosts of the viral community at this developmental stage. Methods Integrating publicly available metagenomic data, a virome repository covering the upper respiratory tract, plasma, and feces was established using viral-like particle enrichment and de novo assembly strategies. Combined with multi-dimensional bioinformatics methods such as clustered regularly interspaced short palindromic repeats(CRISPR)comparison and gene sharing networks, taxonomic annotation of phages, prediction of lifestyle, and prediction of bacterial hosts were achieved. Results A virome dataset comprising 14,555 contigs was constructed, including 509 complete viral genomes(completeness ≥90%)and 340 high-quality complete genomes(completeness ≥95%). A total of six eukaryotic virus families and 23 phage families were identified, of which 71.70% of the phages could not be classified into known virus families. Host prediction covered 96.45% of the phage bacterial hosts, associated with 3,283 bacterial species, including probiotics such as Bifidobacterium and Lactobacillus. Conclusion There are a large number of unclassified phages in the early childhood virome, which form a extensive interaction network with intestinal probiotics, suggesting the high diversity, unique structure, and key potential role of the viral community at this developmental stage in shaping the early microecology.

Key words: Infants and young children, Virus, Bacteriophages, Metagenome, Virome

CLC Number: 

  • R179
[1] Walls Castellanos M, Claud EC. The microbiome, guard or threat to infant health[J]. Trends Mol Med, 2021, 27(12): 1175-1186.
[2] Shkoporov AN, Hill C. Bacteriophages of the human gut: the “known unknown” of the microbiome[J]. Cell Host Microbe, 2019, 25(2): 195-209.
[3] Liang GX, Bushman FD. The human virome: assembly, composition and host interactions[J]. Nat Rev Microbiol, 2021, 19(8): 514-527.
[4] Koonin EV, Dolja VV, Krupovic M. The healthy human virome: from virus-host symbiosis to disease[J]. Curr Opin Virol, 2021, 47: 86-94. doi:10.1016/j.coviro.2021.02.002
[5] 熊卉, 张川, 张伶俐, 等. 中国医疗机构儿童疾病构成的系统评价[J]. 中国循证医学杂志, 2017, 17(8): 973-982. XIONG Hui, ZHANG Chuan, ZHANG Lingli, et al. Diseases constitution of children in Chinese medical institutions: a systematic review[J]. Chinese Journal of Evidence-Based Medicine, 2017, 17(8): 973-982.
[6] Zhang YH, Li F, Zhou YY, et al. Characteristics of plasma Epstein-Barr virus DNA in children with primary infection[J]. Chinese Journal of Pediatrics, 2023, 61(3): 245-249.
[7] Liang GX, Conrad MA, Kelsen JR, et al. Dynamics of the stool virome in very early-onset inflammatory bowel disease[J]. J Crohns Colitis, 2020, 14(11): 1600-1610.
[8] Yinda CK, Vanhulle E, Conceição-Neto N, et al. Gut virome analysis of cameroonians reveals high diversity of enteric viruses, including potential interspecies transmitted viruses[J]. mSphere, 2019, 4(1): e00585-18. doi:10.1128/mSphere.00585-18
[9] Desai C, Handley SA, Rodgers R, et al. Growth velocity in children with Environmental Enteric Dysfunction is associated with specific bacterial and viral taxa of the gastrointestinal tract in Malawian children[J]. PLoS Negl Trop Dis, 2020, 14(6): e0008387. doi:10.1371/journal.pntd.0008387
[10] Vehik K, Lynch KF, Wong MC, et al. Prospective virome analyses in young children at increased genetic risk for type 1 diabetes[J]. Nat Med, 2019, 25(12): 1865-1872.
[11] Gregory AC, Zablocki O, Zayed AA, et al. The gut virome databasereveals age-dependent patterns of virome diversity in the human gut [J]. Cell Host Microbe, 2020, 28(5): 724-740.
[12] Hanson MA, Gluckman PD. Early developmental conditioning of later health and disease: physiology or pathophysiology?[J]. Physiol Rev, 2014, 94(4): 1027-1076.
[13] Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data[J]. Bioinformatics, 2014, 30(15): 2114-2120.
[14] Li DH, Liu CM, Luo RB, et al. MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph[J]. Bioinformatics, 2015, 31(10): 1674-1676.
[15] Gurevich A, Saveliev V, Vyahhi N, et al. QUAST: quality assessment tool for genome assemblies[J]. Bioinformatics, 2013, 29(8): 1072-1075.
[16] Guo JR, Bolduc B, Zayed AA, et al. VirSorter2: a multi-classifier, expert-guided approach to detect diverse DNA and RNA viruses[J]. Microbiome, 2021, 9(1): 37. doi:10.1186/s40168-020-00990-y
[17] Ren J, Ahlgren NA, Lu YY, et al. VirFinder: a novel k-mer based tool for identifying viral sequences from assembled metagenomic data[J]. Microbiome, 2017, 5(1): 69. doi:10.1186/s40168-017-0283-5
[18] Simão FA, Waterhouse RM, Ioannidis P, et al. BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs[J]. Bioinformatics, 2015, 31(19): 3210-3212.
[19] Paez-Espino D, Pavlopoulos GA, Ivanova NN, et al. Nontargeted virus sequence discovery pipeline and virus clustering for metagenomic data[J]. Nat Protoc, 2017, 12(8): 1673-1682.
[20] Nayfach S, Camargo AP, Schulz F, et al. CheckV assesses the quality and completeness of metagenome-assembled viral genomes[J]. Nat Biotechnol, 2021, 39(5): 578-585.
[21] Li WZ, Godzik A. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences[J]. Bioinformatics, 2006, 22(13): 1658-1659.
[22] Shang JY, Peng C, Liao HR, et al. PhaBOX: a web server for identifying and characterizing phage contigs in metagenomic data[J]. Bioinform Adv, 2023, 3(1): vbad101. doi:10.1093/bioadv/vbad101
[23] Hyatt D, Chen GL, Locascio PF, et al. Prodigal: prokaryotic gene recognition and translation initiation site identification[J]. BMC Bioinformatics, 2010, 11: 119. doi:10.1186/1471-2105-11-119
[24] Jang HB, Bolduc B, Zablocki O, et al. Taxonomic assignment of uncultivated prokaryotic virus genomes is enabled by gene-sharing networks[J]. Nat Biotechnol, 2019, 37(6): 632-639.
[25] Buchfink B, Xie C, Huson DH. Fast and sensitive protein alignment using DIAMOND[J]. Nat Methods, 2015, 12(1): 59-60.
[26] Stewart CJ, Ajami NJ, O’Brien JL, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study[J]. Nature, 2018, 562(7728): 583-588.
[27] Liang GX, Zhao CY, Zhang HJ, et al. The stepwise assembly of the neonatal virome is modulated by breastfeeding[J]. Nature, 2020, 581(7809): 470-474.
[28] Shah SA, Deng L, Thorsen J, et al. Expanding known viral diversity in the healthy infant gut[J]. Nat Microbiol, 2023, 8(5): 986-998.
[29] McCann A, Ryan FJ, Stockdale SR, et al. Viromes of one year old infants reveal the impact of birth mode on microbiome diversity[J]. PeerJ, 2018, 6: e4694. doi:10.7717/peerj.4694
[30] Pannaraj PS, Ly M, Cerini C, et al. Shared and distinct features of human milk and infant stool viromes[J]. Front Microbiol, 2018, 9: 1162. doi:10.3389/fmicb.2018.01162
[31] Beller L, Deboutte W, Vieira-Silva S, et al. The virota and its transkingdom interactions in the healthy infant gut[J]. Proc Natl Acad Sci USA, 2022, 119(13): e2114619119. doi:10.1073/pnas.2114619119
[32] Rivera-Gutiérrez X, Morán P, Taboada B, et al. The fecal and oropharyngeal eukaryotic viromes of healthy infants during the first year of life are personal[J]. Sci Rep, 2023, 13(1): 938. doi:10.1038/s41598-022-26707-9
[33] Siqueira JD, Dominguez-Bello MG, Contreras M, et al. Complex virome in feces from Amerindian children in isolated Amazonian villages[J]. Nat Commun, 2018, 9(1): 4270. doi:10.1038/s41467-018-06502-9
[34] Li H, Wang H, Ju HM, et al. Comparison of gut viral communities in children under 5 years old and newborns[J]. Virol J, 2023, 20(1): 52. doi:10.1186/s12985-023-02013-2
[35] Walters WA, Granados AC, Ley C, et al. Longitudinal comparison of the developing gut virome in infants and their mothers[J]. Cell Host Microbe, 2023, 31(2): 187-198.
[36] Lim ES, Zhou YJ, Zhao GY, et al. Early life dynamics of the human gut virome and bacterial microbiome in infants[J]. Nat Med, 2015, 21(10): 1228-1234.
[37] Reyes A, Blanton LV, Cao S, et al. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition[J]. Proc Natl Acad Sci USA, 2015, 112(38): 11941-11946.
[38] Zhao GY, Vatanen T, Droit L, et al. Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children[J]. Proc Natl Acad Sci USA, 2017, 114(30): e6166-e6175.
[39] Tan SK, Granados AC, Bouquet J, et al. Metagenomic sequencing of stool samples in Bangladeshi infants: virome association with poliovirus shedding after oral poliovirus vaccination[J]. Sci Rep, 2020, 10(1): 15392. doi:10.1038/s41598-020-71791-4
[40] Liang GX, Bushman FD. The human virome: assembly, composition and host interactions[J]. Nat Rev Microbiol, 2021, 19(8): 514-527.
[41] Zhang T, Breitbart M, Lee WH, et al. RNA viral community in human feces: prevalence of plant pathogenic viruses[J]. PLoS Biol, 2006, 4(1): e3. doi:10.1371/journal.pbio.0040003
[42] Bushman F, Liang GX. Assembly of the virome in newborn human infants[J]. Curr Opin Virol, 2021, 48: 17-22. doi:10.1016/j.coviro.2021.03.004
[43] Shi M, Lin XD, Tian JH, et al. Redefining the invertebrate RNA virosphere[J]. Nature, 2016, 540(7634): 539-543.
[44] Starr EP, Nuccio EE, Pett-Ridge J, et al. Metatranscriptomic reconstruction reveals RNA viruses with the potential to shape carbon cycling in soil[J]. Proc Natl Acad Sci USA, 2019, 116(51): 25900-25908.
[45] Pleška M, Lang M, Refardt D, et al. Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity[J]. Nat Ecol Evol, 2018, 2(2): 359-366.
[46] Tisza MJ, Lloyd RE, Hoffman K, et al. Longitudinal phage-bacteria dynamics in the early life gut microbiome[J]. Nat Microbiol, 2025, 10(2): 420-430.
[1] WANG Shan, LIU Wei, FENG Qiang, FAN Yingying, LIU Haixia, DUAN Yanhua, WEN Hongling, JIAO Boyan. Whole genome characterization analysis of Coxsackievirus A6 in Jining in 2021 [J]. Journal of Shandong University (Health Sciences), 2025, 63(9): 92-101.
[2] DING Xiaoman, LYU Yan, SUN Jiawen, ZHAO Baotian, QI Na, JIAO Haitao. Epidemiological and genotyping characteristics of human rhinovirus among influenza-like illness in children in Jinan from March 2019 to February 2024 [J]. Journal of Shandong University (Health Sciences), 2025, 63(7): 102-108.
[3] GE Xue, ZHAO Hongyan. Effect of herpesvirus infection on clinical prognosis and respiratory microbiota in patients with severe pneumonia [J]. Journal of Shandong University (Health Sciences), 2025, 63(6): 27-37.
[4] ZHANG Yushuang, WU Juanli, GAO Han, ZHANG Yiheng, LI Tao, WANG Lei. HBV RNA status and changes after intervention in HBeAg-positive chronic hepatitis B patients with low level viremia [J]. Journal of Shandong University (Health Sciences), 2025, 63(3): 85-91.
[5] WEI Jiacheng, YANG Baozhong, WEI Wei, XUE Yating, CUI Chenlong, FANG Jun. MicroRNA-210-3p inhibits inflammatory pain in rats by regulation ten-eleven translocation 2 expression [J]. Journal of Shandong University (Health Sciences), 2024, 62(6): 17-29.
[6] WANG Yumiao, CUI Xiaopei, ZHANG Hongyu. Short-term efficacy and safety of anticoagulant therapy in elderly patients with corona virus disease 2019 [J]. Journal of Shandong University (Health Sciences), 2024, 62(12): 21-31.
[7] SHI Jun, NIU Zijie, WANG Jun, MA Lijing, XI Chunhua, XIAO Yang. Clinical features and anesthetic concerns in pulmonary dissemination of juvenile-onset recurrent respiratory papillomatosis [J]. Journal of Shandong University (Health Sciences), 2024, 62(12): 82-89.
[8] CHEN Yingjun, LIU Tonggang. Comprehensive bioinformatics analysis to identify differentially expressed genes for aberrant methylation modification in HBV-associated HCC [J]. Journal of Shandong University (Health Sciences), 2023, 61(9): 101-117.
[9] BU Meiling, WANG Jinrong, FENG Mei, SUN Lifeng. Mechanism of FOXM1 in acute exacerbation of asthma induced by respiratory virus infection in mice [J]. Journal of Shandong University (Health Sciences), 2023, 61(6): 1-9.
[10] ZHANG Meng, MA Wei. Trend and disease burden of human immunodeficiency virus/acquired immunodeficiency syndrome in China from 1990 to 2019 [J]. Journal of Shandong University (Health Sciences), 2023, 61(5): 84-89.
[11] WANG Shan, JIAO Boyan, FENG Qiang, DUAN Yanhua, WEN Hongling. Epidemic and whole genome characteristics of coxsackievirus A16 in Jining in 2021 [J]. Journal of Shandong University (Health Sciences), 2023, 61(5): 90-95.
[12] DING Xiaoman, LIU Hui, QI Na, WANG Xin, WU Weihua, SUN Ying, LYU Yan, ZHAO Huailong, ZHAO Hong, ZHAO Baotian, JIAO Haitao, FANG Shisong, LIU Lanzheng. Pathogenic detection and epidemic characteristics of influenza in Shenzhen and Jinan from April 2016 to March 2022 [J]. Journal of Shandong University (Health Sciences), 2023, 61(5): 96-101.
[13] LIU Meng, HOU Congzhe, MA Huanyu, ZHANG Zhen, ZHAO Xinrui, ZHANG Ping, ZHU Lin. Effects of β-estradiol on the proliferation of cervical cancer Hela cells [J]. Journal of Shandong University (Health Sciences), 2023, 61(2): 9-15.
[14] LIU Qingqing, WANG Ningning, CHENG Jun, ZHOU Huajun, CHE Feihu, SUN Qingyang, WANG Yue, ZHANG Yingjie, DAI Yuzhu. Establishment and evaluation of a recombinase-aided amplification for the detection of human adenovirus type 4 [J]. Journal of Shandong University (Health Sciences), 2023, 61(10): 74-82.
[15] HAO Qiang, GAO Qi, ZHAO Ran, WANG Haitao, LIU Zhidong, JIANG Baofa. Effects of ambient temperature and relative humidity on rotavirus diarrhea among children under 5 years old in Shenzhen City during 2014-2016 [J]. Journal of Shandong University (Health Sciences), 2022, 60(2): 89-95.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd