屈爱娜;吴德;

• 1:安徽医科大学第一附属医院

摘要(Abstract)：

随着高通量测序技术的发展，与人体共生的微生物群成为当今研究的热点。肠道微生物群是人体最庞杂且重要的微生态系统，与人体健康密切相关。其中，肠道菌群与疾病的研究是热点，但是人们对肠道病毒群的关注较少。该文对人体肠道病毒宏基因组学的研究进行综述，介绍病毒宏基因组学的基本研究内容，以及研究面临的瓶颈问题，阐述利用宏病毒组学探索健康人体肠道病毒群组成的特征、肠道病毒群与某些人类疾病相关性的研究进展。

关键词(KeyWords)： 宏基因组学;病毒宏基因组学;健康人体肠道病毒群;噬菌体

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 屈爱娜;吴德;

DOI: 10.13242/j.cnki.bingduxuebao.004195

参考文献(References)：

• [1]B?ckhed F,Ley R E,Sonnenburg J L,Peterson D A,Gordon J I. Host-bacterial mutualism in the human intestine[J/OL]. Science,2005,307(5717):1915-1920. DOI:10.1126/science.1104816.
• [2]Alejandro Reyes, Matthew Haynes, Nicole Hanson,Florent E Angly,Andrew C Heath,Forest Rohwer,Jeffrey I Gordon. Viruses in the faecal microbiota of monozygotic twins and their mothers[J/OL]. Nature,2010, 466(7304):334-338. DOI:10.1038/nature09199.
• [3]Shkoporov A N,Hill C. Bacteriophages of the Human Gut:The“Known Unknown”of the Microbiome[J/OL]. Cell Host Microbe, 2019, 25(2):195-209.DOI:10.1016/j.chom.2019.01.017.
• [4]Thomas D S Sutton, Adam G Clooney, Feargal J Ryan,R Paul Ross,Colin Hill. Choice of assembly software has a critical impact on virome characterisation[J/OL]. Microbiome,2019,7(1):12. DOI:10.1186/s40168-019-0626-5.
• [5]Moreno-Gallego J L,Reyes A. Informative Regions In Viral Genomes[J/OL]. Viruses,2021,13(6):1164.DOI:10.3390/v13061164.
• [6]Handelsman J,Rondon M R,Brady S F,Clardy J,Goodman R M. Molecular biological access to the chemistry of unknown soil microbes:a new frontier for natural products[J/OL]. Chem Biol,1998,5(10):R245-R249. DOI:10.1016/s1074-5521(98)90108-9.
• [7]Handelsman J. Metagenomics:application of genomics to uncultured microorganisms[J/OL]. Microbiol Mol Biol Rev, 2004, 68(4):669-685. DOI:10.1128/MMBR.68.4.669-685.2004.
• [8]Aggarwala V, Liang G, Bushman F D. Viral communities of the human gut:metagenomic analysis of composition and dynamics[J/OL]. Mobile DNA,2017,8(1):12. DOI:10.1186/s13100-017-0095-y.
• [9]Yutin N,Makarova K S,Gussow A B,Krupovic M,Segall A,Edwards R A,Koonin E V. Discovery of an expansive bacteriophage family that includes the most abundant viruses from the human gut[J/OL]. Nature Microbiology, 2018, 3(1):38-46. DOI:10.1038/s41564-017-0053-y.
• [10]Reyes A,Semenkovich N P,Whiteson K,Rohwer F,Gordon J I. Going viral:next-generation sequencing applied to phage populations in the human gut[J/OL].Nat Rev Microbiol, 2012, 10(9):607-617. DOI:10.1038/nrmicro2853.
• [11]Warwick-Dugdale J,Solonenko N,Moore K,Chittick L,Gregory A C,Allen M J,Sullivan M B,Temperton B. Long-read metagenomics reveals cryptic and abundant marine viruses[J/OL]. Cold Spring Harbor Laboratory,2018. DOI:10.1101/345041.
• [12]Martinez-Hernandez F,Fornas O,Lluesma Gomez M,Bolduc B,de la Cruz Pe?a M J,Martínez J M,Anton J,Gasol J M,Rosselli R,Rodriguez-Valera F,Sullivan M B, Acinas S G, Martinez-Garcia M. Single-virus genomics reveals hidden cosmopolitan and abundant viruses[J/OL]. Nat Commun,2017,8(1):15892.DOI:10.1038/ncomms15892.
• [13]Lim E S,Zhou Y,Zhao G,Bauer I K,Droit L,Ndao I M,Warner B B,Tarr P I,Wang D,Holtz L R.Early life dynamics of the human gut virome and bacterial microbiome in infants[J/OL]. Nat Med, 2015, 21(10):1228-1234. DOI:10.1038/nm.3950.
• [14]Zhang T,Breitbart M,Lee W H,Run J Q,Wei C L,Soh S W,Hibberd M L,Liu E T,Rohwer F,Ruan Y.RNA Viral Community in Human Feces:Prevalence of Plant Pathogenic Viruses[J/OL]. PLoS Biol,2006,4(1):e3. DOI:10.1371/journal.pbio.0040003.
• [15]Lozupone C A,Stombaugh J I,Gordon J I,Jansson J K,Knight R. Diversity,stability and resilience of the human gut microbiota[J/OL]. Nature, 2012, 489(7415):220-230. DOI:10.1038/nature11550.
• [16]Hoyles L,McCartney A L,Neve H,Gibson G R,Sanderson J D, Heller K J, van Sinderen D.Characterization of virus-like particles associated with the human faecal and caecal microbiota[J/OL]. Res Microbiol,2014,165(10):803-812. DOI:10.1016/j.resmic.2014.10.006.
• [17]Roux S,Hallam S J,Woyke T,Sullivan M B. Viral dark matter and virus–host interactions resolved from publicly available microbial genomes[J/OL]. ELife,2015,4:e08490. DOI:10.7554/eLife.08490.
• [18]Browne H P,Forster S C,Anonye B O,Kumar N,Neville B A,Stares M D,Goulding D,Lawley T D.Culturing of'unculturable'human microbiota reveals novel taxa and extensive sporulation[J/OL]. Nature,2016, 533(7604):543-546. DOI:10.1038/nature17645.
• [19]Guerin E,Shkoporov A,Stockdale S R,Clooney A G,Ryan F J, Sutton T D S, Draper L A, GonzalezTortuero E,Ross R P,Hill C. Biology and Taxonomy of crAss-like Bacteriophages,the Most Abundant Virus in the Human Gut[J/OL]. Cell Host Microbe,2018,24(5):653-664. DOI:10.1016/j.chom.2018.10.002.
• [20]Lepage P,Colombet J,Marteau P,Sime-Ngando T,DoréJ,Leclerc M. Dysbiosis in inflammatory bowel disease:a role for bacteriophages?[J/OL]. Gut,2008,57(3):424-425. DOI:10.1136/gut.2007.134668.
• [21]Mokili J L,Rohwer F,Dutilh B E. Metagenomics and future perspectives in virus discovery[J/OL]. Curr Opin Virol, 2012, 2(1):63-77. DOI:10.1016/j.coviro.2011.12.004.
• [22]Minot S,Bryson A,Chehoud C,Wu G D,Lewis J D,Bushman F D. Rapid evolution of the human gut virome[J/OL]. Proc Natl Acad Sci U S A,2013,110(30):12450-12455. DOI:10.1073/pnas.1300833110.
• [23]Hsu B B,Gibson T E,Yeliseyev V,Liu Q,Lyon L,Bry L,Silver P A,Gerber G K. Dynamic Modulation of the Gut Microbiota and Metabolome by Bacteriophages in a Mouse Model[J/OL]. Cell Host Microbe,2019,25(6):803-814. DOI:10.1016/j.chom.2019.05.001.
• [24]Gogokhia L,Buhrke K,Bell R,Hoffman B,Brown D G, Hanke-Gogokhia C, Ajami N J, Wong M C,Ghazaryan A,Valentine J F,Porter N,Martens E,O'Connell R, Jacob V, Scherl E, Crawford C,Stephens W Z,Casjens S R,Longman R S,Round J L.Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis[J/OL]. Cell Host Microbe, 2019, 25(2):285-299. DOI:10.1016/j.chom.2019.01.008.
• [25]Edwards R A,Vega A A,Norman H M,Ohaeri M,Levi K,Dinsdale EA,Cinek O,Aziz R K,McNair K,Barr J J,Bibby K,Brouns S J J,Cazares A,de Jonge P A, Desnues C, Díaz Mu?oz S L, Fineran P C,Kurilshikov A,Lavigne R,Mazankova K,McCarthy D T,Nobrega F L,Reyes Mu?oz A,Tapia G,Trefault N,Tyakht AV,Vinuesa P, Wagemans J,Zhernakova A,Aarestrup F M,Ahmadov G,Alassaf A,Anton J,Asangba A,Billings E K,Cantu V A,Carlton J M,Cazares D,Cho G S,Condeff T,Cortés P,Cranfield M,Cuevas D A,De la Iglesia R,Decewicz P,Doane M P,Dominy N J,Dziewit L,Elwasila B M,Eren A M,Franz C,Fu J,Garcia-Aljaro C,Ghedin E,Gulino K M,Haggerty J M,Head S R,Hendriksen R S,Hill C,Hy?ty H,Ilina E N,Irwin M T,Jeffries T C,Jofre J, Junge R E, Kelley S T, Khan Mirzaei M,Kowalewski M,Kumaresan D,Leigh S R,Lipson D,Lisitsyna E S,Llagostera M,Maritz J M,Marr L C,McCann A,Molshanski-Mor S,Monteiro S,MoreiraGrez B,Morris M,Mugisha L,Muniesa M,Neve H,Nguyen N P,Nigro O D,Nilsson A S,O'Connell T,Odeh R,Oliver A,Piuri M,Prussin Ii A J,Qimron U,Quan Z X,Rainetova P,Ramírez-Rojas A,Raya R,Reasor K,Rice G A O,Rossi A,Santos R,Shimashita J,Stachler E N,Stene L C,Strain R,Stumpf R,Torres P J,Twaddle A,Ugochi Ibekwe M,Villagra N,Wandro S,White B,Whiteley A,Whiteson K L,Wijmenga C,Zambrano M M,Zschach H,Dutilh B E.Global phylogeography and ancient evolution of the widespread human gut virus crAssphage[J/OL]. Nat Microbiol,2019,4(10):1727-1736. DOI:10.1038/s41564-019-0494-6.
• [26]Pedulla M L,Ford M E,Houtz J M,Karthikeyan T,Wadsworth C,Lewis J A,Jacobs-Sera D,Falbo J,Gross J, Pannunzio N R, Brucker W, Kumar V,Kandasamy J, Keenan L, Bardarov S, Kriakov J,Lawrence J G,Jacobs W R,Hendrix R W,Hatfull G F. Origins of Highly Mosaic Mycobacteriophage Genomes[J/OL]. Cell,2003,113(2):171-182. DOI:10.1016/s0092-8674(03)00233-2.
• [27]Dutilh B E,Cassman N,McNair K,Sanchez S E,Silva G G,Boling L,Barr J J,Speth D R,Seguritan V,Aziz R K,Felts B,Dinsdale E A,Mokili J L,Edwards R A. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes[J/OL]. Nat Commun, 2014, 5(1):4498. DOI:10.1038/ncomms5498.
• [28]Honap T P,Sankaranarayanan K,Schnorr S L,Ozga A T,Warinner C,Lewis C M. Biogeographic study of human gut-associated crAssphage suggests impacts from industrialization and recent expansion[J/OL]. PLoS One,2020,15(1):e226930. DOI:10.1371/journal.pone.0226930.
• [29]McCann A,Ryan F J,Stockdale S R,Dalmasso M,Blake T,Ryan C A,Stanton C,Mills S,Ross P R,Hill C. Viromes of one year old infants reveal the impact of birth mode on microbiome diversity[J/OL]. PeerJ,2018,6:e4694. DOI:10.7717/peerj.4694.
• [30]Shkoporov A N,Ryan F J,Draper L A,Forde A,Stockdale S R,Daly K M,McDonnell S A,Nolan J A,Sutton T D S,Dalmasso M,McCann A,Ross R P,Hill C. Reproducible protocols for metagenomic analysis of human faecal phageomes[J/OL]. Microbiome,2018,6(1):68. DOI:10.1186/s40168-018-0446-z.
• [31]Shkoporov A N,Clooney A G,Sutton T D S,Ryan F J,Daly K M,Nolan J A,McDonnell S A,Khokhlova E V,Draper L A,Forde A,Guerin E,Velayudhan V,Ross R P,Hill C. The Human Gut Virome Is Highly Diverse,Stable,and Individual Specific[J/OL]. Cell Host Microbe,2019,26(4):527-541. DOI:10.1016/j.chom.2019.09.009.
• [32]Manrique P,Bolduc B,Walk S T,van der Oost J,de Vos W M,Young M J. Healthy human gut phageome[J/OL]. Proc Natl Acad Sci U S A,2016,113(37):10400-10405. DOI:10.1073/pnas.1601060113.
• [33]Ly M,Jones M B,Abeles S R,Santiago-Rodriguez T M, Gao J, Chan I C, Ghose C, Pride D T.Transmission of viruses via our microbiomes[J/OL].Microbiome,2016,4(1):64. DOI:10.1186/s40168-016-0212-z.
• [34]Chen L,Wang D,Garmaeva S,Kurilshikov A,Vich Vila A,Gacesa R,Sinha T,Lifelines Cohort Study,Segal E,Weersma R K,Wijmenga C,Zhernakova A,Fu J. The long-term genetic stability and individual specificity of the human gut microbiome[J/OL]. Cell,2021, 184(9):2302-2315. DOI:10.1016/j.cell.2021.03.024.
• [35]Sell T L,Schaberg D R,Fekety F R. Bacteriophage and bacteriocin typing scheme for Clostridium difficile[J/OL]. J Clin Microbiol,1983,17(6):1148-1152. DOI:10.1128/jcm.17.6.1148-1152.1983.
• [36]Norman J M,Handley S A,Baldridge M T,Droit L,Liu C Y,Keller B C,Kambal A,Monaco C L,Zhao G,Fleshner P,Stappenbeck T S,McGovern D P,Keshavarzian A,Mutlu E A,Sauk J,Gevers D,Xavier R J,Wang D,Parkes M,Virgin H W. Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease[J/OL]. Cell,2015,160(3):447-460.DOI:10.1016/j.cell.2015.01.002.
• [37]Cornuault J K,Petit M A,Mariadassou M,Benevides L,Moncaut E,Langella P,Sokol H,De Paepe M.Phages infecting Faecalibacterium prausnitzii belong to novel viral genera that help to decipher intestinal viromes[J/OL]. Microbiome,2018,6(1):65. DOI:10.1186/s40168-018-0452-1.
• [38]Clooney A G,Sutton T D S,Shkoporov A N,Holohan R K,Daly K M,O'Regan O,Ryan F J,Draper L A,Plevy S E,Ross R P,Hill C. Whole-Virome Analysis Sheds Light on Viral Dark Matter in Inflammatory Bowel Disease[J/OL]. Cell Host Microbe,2019,26(6):764-778. DOI:10.1016/j.chom.2019.10.009.
• [39]Rhee S H,Pothoulakis C,Mayer E A. Principles and clinical implications of the brain-gut-enteric microbiota axis[J/OL]. Nat Rev Gastroenterol Hepatol,2009,6(5):306–314. DOI:10.1038/nrgastro.2009.35.
• [40]Carabotti M,Scirocco A,Maselli M A,Severi C. The gut-brain axis:interactions between enteric microbiota,central and enteric nervous systems[J]. Ann Gastroenterol, 2015, 28(2):203-209. PMCID:PMC4367209.
• [41]Tetz G,Brown S M,Hao Y,Tetz V. Parkinson’s disease and bacteriophages as its overlooked contributors[J/OL]. Sci Rep,2018,8(1):10812. DOI:10.1038/s41598-018-29173-4.
• [42]Reyes A,Blanton L V,Cao S,Zhao G,Manary M,Trehan I,Smith M I,Wang D,Virgin H W,Rohwer F,Gordon J I. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition[J/OL]. Proc Natl Acad Sci U S A,2015,112(38):11941-11946.DOI:10.1073/pnas.1514285112.