肠道噬菌体与机体健康的研究进展及临床应用

doi:10.3760/cma.j.issn.1007-1245.2023.17.002

摘要/Abstract

摘要：

肠道微生物被誉为人类“隐形的器官”，对维持机体健康有着重要作用，涵盖细菌、病毒、真菌等成分，其中噬菌体更是肠道病毒组的主要成员。随着近年来宏基因组的应用和细菌耐药性的增加，肠道噬菌体对机体健康的影响以及噬菌体疗法的临床应用成为了国内外研究的重要方向。本文围绕国内外肠道噬菌体研究现状进行讨论，探讨噬菌体对机体健康的影响并结合噬菌体疗法的临床应用做一综述。

关键词:

噬菌体, 肠道菌群, 疾病, 健康, 进展

Abstract:

Intestinal microorganisms, known as "invisible organs" of human beings, play an important role in maintaining the health of the body, covering bacteria, viruses, fungi, and other components, among which bacteriophage is the main member of enterovirus group. With the application of metagenomics and the increase of bacterial resistance in recent years, the impact of intestinal bacteriophage on human health and the clinical application of bacteriophage therapy have become an important research direction worldwide. In this paper, the research status of intestinal bacteriophage is summarized, and the impact of bacteriophage on human health and clinical application are reviewed.

Key words:

Bacteriophage, Gut microbiota, Disease, Health, Progress

罗梅娟张又祥欧巧群王丽娜.

肠道噬菌体与机体健康的研究进展及临床应用 [J]. 国际医药卫生导报, 2023, 29(17): 2373-2377.

Luo Meijuan, Zhang Youxiang, Ou Qiaoqun, Wang Lina.

Research progress and clinical application of intestinal bacteriophage and human health [J]. International Medicine and Health Guidance News, 2023, 29(17): 2373-2377.

参考文献

[1] Altveş S, Yildiz HK, Vural HC. Interaction of the microbiota with the human body in health and diseases[J]. Biosci Microbiota Food Health, 2020, 39(2):23-32. DOI: 10.12938/bmfh.19-023.
[2] Fujimura KE, Slusher NA, Cabana MD, et al. Role of the gut microbiota in defining human health[J]. Expert Rev Anti Infect Ther, 2010, 8(4):435-454. DOI: 10.1586/eri.10.14.
[3] Gindin M, Febvre HP, Rao S, et al. Bacteriophage for gastrointestinal health (PHAGE) study: evaluating the safety and tolerability of supplemental bacteriophage consumption[J]. J Am Coll Nutr, 2019, 38(1):68-75. DOI: 10.1080/07315724.2018.1483783.
[4] Dion MB, Oechslin F, Moineau S. Phage diversity, genomics and phylogeny[J]. Nat Rev Microbiol, 2020, 18(3):125-138. DOI: 10.1038/s41579-019-0311-5.
[5] Dutilh BE, Cassman N, McNair K, et al. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes[J]. Nat Commun, 2014, 5:4498. DOI: 10.1038/ncomms5498.
[6] Norman JM, Handley SA, Baldridge MT, et al. Disease-specific alterations in the enteric virome in inflammatory bowel disease[J]. Cell, 2015, 160(3):447-460. DOI: 10.1016/j.cell.2015.01.002.
[7] Manrique P, Bolduc B, Walk ST, et al. Healthy human gut phageome[J]. Proc Natl Acad Sci U S A, 2016, 113(37):10400-10405. DOI: 10.1073/pnas.1601060113.
[8] Sausset R, Petit MA, Gaboriau-Routhiau V, et al. New insights into intestinal phages[J]. Mucosal Immunol, 2020, 13(2):205-215. DOI: 10.1038/s41385-019-0250-5.
[9] Safari F, Sharifi M, Farajnia S, et al. The interaction of phages and bacteria: the co-evolutionary arms race[J]. Crit Rev Biotechnol, 2020, 40(2):119-137. DOI: 10.1080/07388551.2019.1674774.
[10] Cornuault JK, Petit MA, Mariadassou M, et al. Phages infecting Faecalibacterium prausnitzii belong to novel viral genera that help to decipher intestinal viromes[J]. Microbiome, 2018, 6(1):65. DOI: 10.1186/s40168-018-0452-1.
[11] Stern A, Mick E, Tirosh I, et al. CRISPR targeting reveals a reservoir of common phages associated with the human gut microbiome[J]. Genome Res, 2012, 22(10):1985-1994. DOI: 10.1101/gr.138297.112.
[12] Santiago-Rodriguez TM, Hollister EB. Human virome and disease: high-throughput sequencing for virus discovery, identification of phage-bacteria dysbiosis and development of therapeutic approaches with emphasis on the human gut[J]. Viruses, 2019, 11(7):656. DOI: 10.3390/v11070656.
[13] Taylor VL, Fitzpatrick AD, Islam Z, et al. The diverse impacts of phage morons on bacterial fitness and virulence[J]. Adv Virus Res, 2019, 103:1-31. DOI: 10.1016/bs.aivir.2018.08.001.
[14] Wahl A, Battesti A, Ansaldi M. Prophages in Salmonella enterica: a driving force in reshaping the genome and physiology of their bacterial host? [J]. Mol Microbiol, 2019, 111(2):303-316. DOI: 10.1111/mmi.14167.
[15] Garmaeva S, Sinha T, Kurilshikov A, et al. Studying the gut virome in the metagenomic era: challenges and perspectives[J]. BMC Biol, 2019, 17(1):84. DOI: 10.1186/s12915-019-0704-y.
[16] Zuo T, Wong SH, Lam K, et al. Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome[J]. Gut, 2018, 67(4):634-643. DOI: 10.1136/gutjnl-2017-313952.
[17] Barr JJ, Auro R, Furlan M, et al. Bacteriophage adhering to mucus provide a non-host-derived immunity[J]. Proc Natl Acad Sci U S A, 2013, 110(26):10771-10776. DOI: 10.1073/pnas.1305923110.
[18] Gogokhia L, Buhrke K, Bell R, et al. Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis[J]. Cell Host Microbe, 2019, 25(2):285-299.e8. DOI: 10.1016/j.chom.2019.01.008.
[19] Górski A, Międzybrodzki R, Borysowski J, et al. Phage as a modulator of immune responses: practical implications for phage therapy[J]. Adv Virus Res, 2012, 83:41-71. DOI: 10.1016/B978-0-12-394438-2.00002-5.
[20] Canfield GS, Duerkop BA. Molecular mechanisms of enterococcal-bacteriophage interactions and implications for human health[J]. Curr Opin Microbiol, 2020, 56:38-44. DOI: 10.1016/j.mib.2020.06.003.
[21] Segall AM, Roach DR, Strathdee SA. Stronger together? Perspectives on phage-antibiotic synergy in clinical applications of phage therapy[J]. Curr Opin Microbiol, 2019, 51:46-50. DOI: 10.1016/j.mib.2019.03.005.
[22] Seo SU, Kweon MN. Virome-host interactions in intestinal health and disease[J]. Curr Opin Virol, 2019, 37:63-71. DOI: 10.1016/j.coviro.2019.06.003.
[23] 赵盈,宋光.炎症性肠病:微生物-宿主因素的研究进展[J].现代消化及介入诊疗,2020,25(11):1548-1551. DOI:10.3969/j.issn.1672-2159.2020.11.033.
[24] Zuo T, Lu XJ, Zhang Y, et al. Gut mucosal virome alterations in ulcerative colitis[J]. Gut, 2019, 68(7):1169-1179. DOI: 10.1136/gutjnl-2018-318131.
[25] Yang JY, Kim MS, Kim E, et al. Enteric viruses ameliorate gut inflammation via toll-like receptor 3 and toll-like receptor 7-mediated interferon-β production[J]. Immunity, 2016, 44(4):889-900. DOI: 10.1016/j.immuni.2016.03.009.
[26] Van Belleghem JD, Clement F, Merabishvili M, et al. Pro- and anti-inflammatory responses of peripheral blood mononuclear cells induced by Staphylococcus aureus and Pseudomonas aeruginosa phages[J]. Sci Rep, 2017, 7(1):8004. DOI: 10.1038/s41598-017-08336-9.
[27] Kato I, Zhang J, Sun J. Bacterial-viral interactions in human orodigestive and female genital tract cancers: a summary of epidemiologic and laboratory evidence[J]. Cancers (Basel), 2022, 14(2):425. DOI: 10.3390/cancers14020425.
[28] 孙中,艾江.肠道菌群失调与结直肠癌关系的研究进展[J].现代消化及介入诊疗,2021,26(4):530-533. DOI:10.3969/j.issn.1672-2159.2021.04.029.
[29] Nakatsu G, Zhou H, Wu WKK, et al. Alterations in enteric virome are associated with colorectal cancer and survival outcomes[J]. Gastroenterology, 2018, 155(2):529-541.e5. DOI: 10.1053/j.gastro.2018.04.018.
[30] Hannigan GD, Duhaime MB, Ruffin MT 4th, et al. Diagnostic potential and interactive dynamics of the colorectal cancer virome[J]. mBio, 2018, 9(6):e02248-18. DOI: 10.1128/mBio.02248-18.
[31] Zheng DW, Dong X, Pan P, et al. Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy[J]. Nat Biomed Eng, 2019, 3(9):717-728. DOI: 10.1038/s41551-019-0423-2.
[32] Ma Y, You X, Mai G, et al. A human gut phage catalog correlates the gut phageome with type 2 diabetes[J]. Microbiome, 2018, 6(1):24. DOI: 10.1186/s40168-018-0410-y.
[33] Zhao G, Vatanen T, Droit L, et al. Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children[J]. Proc Natl Acad Sci U S A, 2017, 114(30):E6166-E6175. DOI: 10.1073/pnas.1706359114.
[34] Clokie MRJ. Microbial clues to a liver disease[J]. Nature, 2019, 575(7783):451-453. DOI: 10.1038/d41586-019-　03417-3.
[35] Duan Y, Llorente C, Lang S, et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease[J]. Nature, 2019, 575(7783):505-511. DOI: 10.1038/s41586-019-1742-x.
[36] Tetz G, Brown SM, Hao Y, et al. Parkinson's disease and bacteriophages as its overlooked contributors[J]. Sci Rep, 2018, 8(1):10812. DOI: 10.1038/s41598-018-29173-4.
[37] Yolken RH, Severance EG, Sabunciyan S, et al. Metagenomic sequencing indicates that the oropharyngeal phageome of individuals with schizophrenia differs from that of controls[J]. Schizophr Bull, 2015, 41(5):1153-1161. DOI: 10.1093/schbul/sbu197.
[38] Sabino J, Hirten RP, Colombel JF. Review article: bacteriophages in gastroenterology-from biology to clinical applications[J]. Aliment Pharmacol Ther, 2020, 51(1):53-63. DOI: 10.1111/apt.15557.
[39] Weber-Dabrowska B, Mulczyk M, Górski A. Bacteriophage therapy of bacterial infections: an update of our institute's experience[J]. Arch Immunol Ther Exp (Warsz), 2000, 48(6):547-551.
[40] Żaczek M, Weber-Dąbrowska B, Międzybrodzki R, et al. Phage therapy in Poland - a centennial journey to the first ethically approved treatment facility in Europe[J]. Front Microbiol, 2020, 11:1056. DOI: 10.3389/fmicb.2020.　01056.
[41] Ott SJ, Waetzig GH, Rehman A, et al. Efficacy of sterile fecal filtrate transfer for treating patients with clostridium difficile infection[J]. Gastroenterology, 2017, 152(4):799-811.e7. DOI: 10.1053/j.gastro.2016.11.010.
[42] Dedrick RM, Guerrero-Bustamante CA, Garlena RA, et al. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus[J]. Nat Med, 2019, 25(5):730-733. DOI: 10.1038/s41591-019-0437-z.
[43] Khawaldeh A, Morales S, Dillon B, et al. Bacteriophage therapy for refractory Pseudomonas aeruginosa urinary tract infection[J]. J Med Microbiol, 2011, 60(Pt 11):1697-1700. DOI: 10.1099/jmm.0.029744-0.
[44] Leszczyński P, Weber-Dabrowska B, Kohutnicka M, et al. Successful eradication of methicillin-resistant Staphylococcus aureus (MRSA) intestinal carrier status in a healthcare worker--case report[J]. Folia Microbiol (Praha), 2006, 51(3):236-238. DOI: 10.1007/BF02932128.
[45] Bao J, Wu N, Zeng Y, et al. Non-active antibiotic and bacteriophage synergism to successfully treat recurrent urinary tract infection caused by extensively drug-resistant Klebsiella pneumoniae[J]. Emerg Microbes Infect, 2020, 9(1):771-774. DOI: 10.1080/22221751. 2020.1747950.
[46] Leitner L, Sybesma W, Chanishvili N, et al. Bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: a randomized, placebo-controlled, double-blind clinical trial[J]. BMC Urol, 2017, 17(1):90. DOI: 10.1186/s12894-017- 0283-6.
[47] Ooi ML, Drilling AJ, Morales S, et al. Safety and tolerability of bacteriophage therapy for chronic rhinosinusitis due to Staphylococcus aureus[J]. JAMA Otolaryngol Head Neck Surg, 2019, 145(8):723-729. DOI: 10.1001/jamaoto.2019. 1191.
[48] Xu J, Yang H, Bi Y, et al. Activity of the chimeric lysin ClyR against common gram-positive oral microbes and its anticaries efficacy in rat models[J]. Viruses, 2018, 10(7):380. DOI: 10.3390/v10070380.
[49] Li W, Yang H, Gong Y, et al. Effects of a chimeric lysin against planktonic and sessile enterococcus faecalis hint at potential application in endodontic therapy[J]. Viruses, 2018, 10(6):290. DOI: 10.3390/v10060290.
[50] Jault P, Leclerc T, Jennes S, et al. Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial[J]. Lancet Infect Dis, 2019, 19(1):35-45. DOI: 10.1016/S1473-3099(18)30482-1.
[51] 邹秀月,蔡德周.噬菌体治疗细菌性疾病的研究进展及发展方向[J].中国感染控制杂志,2019,18(9):888-892. DOI:10.12138/j.issn.1671-9638.20194491.
[52] Kortright KE, Chan BK, Koff JL, et al. Phage therapy: a renewed approach to combat antibiotic-resistant bacteria[J]. Cell Host Microbe, 2019, 25(2):219-232. DOI: 10.1016/j.chom.2019.01.014.
[53] Kaur G, Agarwal R, Sharma RK. Bacteriophage therapy for critical and high-priority antibiotic-resistant bacteria and phage cocktail-antibiotic formulation perspective[J]. Food Environ Virol, 2021, 13(4):433-446. DOI: 10.1007/s12560-021-09483-z.
[54] Azam AH, Tanji Y. Bacteriophage-host arm race: an update on the mechanism of phage resistance in bacteria and revenge of the phage with the perspective for phage therapy[J]. Appl Microbiol Biotechnol, 2019, 103(5):2121-2131. DOI: 10.1007/s00253-019-09629-x.
[55] Liu D, Van Belleghem JD, de Vries CR, et al. The safety and toxicity of phage therapy: a review of animal and clinical studies[J]. Viruses, 2021, 13(7):1268. DOI: 10.3390/v13071268.