운동영양학회지 (Korean Journal of Exercise Nutrition)

한국운동영양학회
권호 표지
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Interplays between human microbiota and microRNAs in COVID-19 pathogenesis: a literature review

  • 투고 : 2021.06.04
  • 심사 : 2021.06.24
  • 발행 : 2021.06.30
⟨ 이전 논문 다음 논문 ⟩

초록

[Purpose] Recent studies have shown that COVID-19 is often associated with altered gut microbiota composition and reflects disease severity. Furthermore, various reports suggest that the interaction between COVID-19 and host-microbiota homeostasis is mediated through the modulation of microRNAs (miRNAs). Thus, in this review, we aim to summarize the association between human microbiota and miRNAs in COVID-19 pathogenesis. [Methods] We searched for the existing literature using the keywords such "COVID-19 or microbiota," "microbiota or microRNA," and "COVID-19 or probiotics" in PubMed until March 31, 2021. Subsequently, we thoroughly reviewed the articles related to microbiota and miRNAs in COVID-19 to generate a comprehensive picture depicting the association between human microbiota and microRNAs in the pathogenesis of COVID-19. [Results] There exists strong experimental evidence suggesting that the composition and diversity of human microbiota are altered in COVID-19 patients, implicating a bidirectional association between the respiratory and gastrointestinal tracts. In addition, SARS-CoV-2 encoded miRNAs and host cellular microRNAs modulated by human microbiota can interfere with viral replication and regulate host gene expression involved in the initiation and progression of COVID-19. These findings suggest that the manipulation of human microbiota with probiotics may play a significant role against SARS-CoV-2 infection by enhancing the host immune system and lowering the inflammatory status. [Conclusion] The human microbiota-miRNA axis can be used as a therapeutic approach for COVID-19. Hence, further studies are needed to investigate the exact molecular mechanisms underlying the regulation of miRNA expression in human microbiota and how these miRNA profiles mediate viral infection through host-microbe interactions.

키워드

과제정보

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2020R1F1A1049665).

참고문헌

  1. Islam MR, Hoque MN, Rahman MS, Alam A, Akther M, Puspo JA, Akter S, Sultana M, Crandall KA, Hossain MA. Genome-wide analysis of SARS-CoV-2 virus strains circulating worldwide implicates heterogeneity. Sci Rep. 2020;10:14004. https://doi.org/10.1038/s41598-020-70812-6
  2. Paules CI, Marston HD, Fauci AS. Coronavirus infections-more than just the common cold. JAMA. 2020;323:707-8. https://doi.org/10.1001/jama.2020.0757
  3. Harrison AG, Lin T, Wang P. Mechanisms of SARS-CoV-2 transmission and pathogenesis. Trends Immunol. 2020;41:1100-15. https://doi.org/10.1016/j.it.2020.10.004
  4. Wang Q, Zhang Y, Wu L, Niu S, Song C, Zhang Z, Lu G, Qiao C, Hu Y, Yuen KY, Wang Q, Zhou H, Yan J, Qi J. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell. 2020;181:894-904. https://doi.org/10.1016/j.cell.2020.03.045
  5. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271-80. https://doi.org/10.1016/j.cell.2020.02.052
  6. Tang Y, Liu J, Zhang D, Xu Z, Ji J, Wen C. Cytokine storm in COVID-19: the current evidence and treatment strategies. Front Immunol. 2020;11:1708. https://doi.org/10.3389/fimmu.2020.01708
  7. Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY. Freedberg DE, Kirtane AJ, Parikh S, Maurer MS, Nordvig AS, Accili D, Bathon JM, Mohan S, Bauer KA, Leon MB, Krumholz HM, Uriel N, Mehra MR, Elkind MSV, Stone GW, Schwartz A, Ho DD, Pilezikian JPB, Landry DW. Extrapulmonary manifestations of COVID-19. Nat Med. 2020;26:1017-32. https://doi.org/10.1038/s41591-020-0968-3
  8. Redd WD, Zhou JC, Hathorn KE, McCarty TR, Bazarbashi AN, Thompson CC, Shen L, Chan WW. Prevalence and characteristics of gastrointestinal symptoms in patients with severe acute respiratory syndrome coronavirus 2 infection in the United States: a multicenter cohort study. Gastroenterology. 2020;159:765-7. https://doi.org/10.1053/j.gastro.2020.04.045
  9. Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, Tan. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020;323:1843-4.
  10. Chen Y, Chen L, Deng Q, Zhang G, Wu K, Ni L, Yang Y, Liu B, Wang W, Wei C, Yang J, Ye G, Cheng Z. The presence of SARS-CoV-2 RNA in the feces of COVID-19 patients. J Med Virol. 2020;92:833-40. https://doi.org/10.1002/jmv.25825
  11. Han MS, Seong MW, Kim N, Shin S, Cho SI, Park H, Kim TS, Park SS, Choi EH. Viral RNA load in mildly symptomatic and asymptomatic children with COVID-19, Seoul, South Korea. Emerg Infect Dis. 2020;26:2497-9. https://doi.org/10.3201/eid2610.202449
  12. Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207-14. https://doi.org/10.1038/nature11234
  13. Brooks AW, Priya S, Blekhman R, Bordenstein SR. Gut microbiota diversity across ethnicities in the United States. PLoS Biol. 2018;16:e2006842. https://doi.org/10.1371/journal.pbio.2006842
  14. Durack J, Lynch SV. The gut microbiome: relationships with disease and opportunities for therapy. J Exp Med. 2019;216:20-40. https://doi.org/10.1084/jem.20180448
  15. Manor O, Dai CL, Kornilov SA, Smith B, Price ND, Lovejoy JC, Gibbons SM, Magis AT. Health and disease markers correlate with gut microbiome composition across thousands of people. Nat Commun. 2020;11:5206. https://doi.org/10.1038/s41467-020-18871-1
  16. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Nageshwar Reddy D. Role of the normal gut microbiota. World J Gastroenterol. 2015;21:8787-803. https://doi.org/10.3748/wjg.v21.i29.8787
  17. Hasan N, Yang H. Factors affecting the composition of the gut microbiota, and its modulation. PeerJ. 2019;7:e7502. https://doi.org/10.7717/peerj.7502
  18. Burchill E, Lymberopoulos E, Menozzi E, Budhdeo S, McIlroy JR, Macnaughtan J, Sharma N. The unique impact of COVID-19 on human gut microbiome research. Front Med. (Lausanne) 2021;8:652464. https://doi.org/10.3389/fmed.2021.652464
  19. Thevaranjan N, Puchta A, Schulz C, Naidoo A, Szamosi JC, Verschoor CP, Loukov D, Schenck LP, Jury J, Foley KP, Schertzer JD, Larche MJ, Davidson DJ, Verdu EF, Surette MG, Bowdish DM. Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction. Cell Host Microbe. 2017;21:455-66. https://doi.org/10.1016/j.chom.2017.03.002
  20. Gu S, Chen Y, Wu Z, Chen Y, Gao H, Lv L, Guo F, Zhang X, Luo R, Huang C, Lu H, Zheng B, Zhang J, Yan R, Zhang H, Jiang H, Xu Q, Guo J, Gong Y, Tng L, Li L. Alterations of the gut microbiota in patients with coronavirus disease 2019 or H1N1 influenza. Clin Infect Dis. 2020;71:2669-78. https://doi.org/10.1093/cid/ciaa709
  21. Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, Wan Y, Chung ACK, Cheung CP, Chen N, Lai CKC, Chen Z, Tso EYK, Fung KSC, Chan V, Ling L, Joynt G, Hui DSC, Chan FKL, Chan PKS, Na SC. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology. 2020;159:944-55. https://doi.org/10.1053/j.gastro.2020.05.048
  22. Yeoh YK, Zuo T, Lui GC, Zhang F, Liu Q, Li AY, Chung AC, Cheung CP, Tso EY, Fung KS, Chan V, Ling L, Joynt G, Hui DSC, Chow KM, Ng SSS, Li TCM, Ng RW, Yip TC, Wong GLH, Chan FK, Wong CK, Chan PK, Ng SC. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021;70:698-706. https://doi.org/10.1136/gutjnl-2020-323020
  23. Kim HS. Do an altered gut microbiota and an associated leaky gut affect COVID-19 severity? mBio. 2021;12:e03022-20.
  24. Din AU, Mazhar M, Waseem M, Ahmad W, Bibi A, Hassan A, Ali N, Gang W, Qian G, Ullah R, Shah T, Ullah M, Khan I, Nisar MF, Wu J. SARS-CoV-2 microbiome dysbiosis linked disorders and possible probiotics role. Biomed Pharmacother. 2021;133:110947. https://doi.org/10.1016/j.biopha.2020.110947
  25. Chhibber-Goel J, Gopinathan S, Sharma A. Interplay between severities of COVID-19 and the gut microbiome: implications of bacterial co-infections? Gut Pathog. 2021;13:14. https://doi.org/10.1186/s13099-021-00407-7
  26. He Y, Wen Q, Yao F, Xu D, Huang Y, Wang. Gut-lung axis: the microbial contributions and clinical implications. Crit Rev Microbiol. 2017;43:81-95. https://doi.org/10.1080/1040841X.2016.1176988
  27. Wypych TP, Wickramasinghe LC, Marsland BJ. The influence of the microbiome on respiratory health. Nat Immunol. 2019;20:1279-90. https://doi.org/10.1038/s41590-019-0451-9
  28. Shen Z, Xiao Y, Kang L, Ma W, Shi L, Zhang L, Zhou Z, Yang J, Zhong J, Yang D, Guo L, Zhang G, Li H, Xu Y, Chen M, Gao Z, Wang J, Ren L, Li M. Genomic diversity of severe acute respiratory syndrome-coronavirus 2 in patients with Coronavirus disease 2019. Clin Infect Dis. 2020;71:713-20. https://doi.org/10.1093/cid/ciaa203
  29. Fan J, Li X, Gao Y, Zhou J, Wang S, Huang B, Wu J, Cao Q, Chen Y, Wang Z, Luo D, Zhou T, Li R, Shang Y, Nie X. The lung tissue microbiota features of 20 deceased patients with COVID-19. J Infect. 2020;81:e64-7. https://doi.org/10.1016/j.jinf.2020.06.047
  30. Hoque MN, Rahman MS, Ahmed R, Hossain MS, Islam MS, Islam T, Hossain MA, Siddiki AZ. Diversity and genomic determinants of the microbiomes associated with COVID-19 and non-COVID respiratory diseases. Gene Rep. 2021;23:101200. https://doi.org/10.1016/j.genrep.2021.101200
  31. De Maio F, Posteraro B, Ponziani FR, Cattani P, Gasbarrini A, Sanguinetti M. Nasopharyngeal microbiota profiling of SARS-CoV-2 infected patients. Biol Proced Online. 2020;22:18. https://doi.org/10.1186/s12575-020-00131-7
  32. Budding AE, Sieswerda E, Wintermans BB, Bos MP. An age dependent pharyngeal microbiota signature associated with SARS-CoV-2 infection (4/21/2020). Available at SSRN: https://ssrn.com/abstract=3582780 or http://dx.doi.org/10.2139/ssrn.3582780.
  33. de Oliveira GLV, Oliveira CNS, Pinzan CF, de Salis LVV, Cardoso CRB. Microbiota modulation of the gut-lung Axis in COVID-19. Front Immunol. 2021;12:635471. https://doi.org/10.3389/fimmu.2021.635471
  34. Donaldson GP, Lee SM, Mazmanian SK. Gut biogeography of the bacterial microbiota. Nat Rev Microbiol. 2016;14:20-32. https://doi.org/10.1038/nrmicro3552
  35. Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodriguez L. SARS-CoV-2 infection: the role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev. 2020;54:62-75. https://doi.org/10.1016/j.cytogfr.2020.06.001
  36. Gou W, Fu Y, Yue L, Chen G-D, Cai X, Shuai M, Xu F, Yi X, Chen H, Zhu YJ, Xiao ML, Jiang Z, Miao Z, Xiao C, Shen B, Wu X, Zhao H, Ling W, Wang J, Chen YM, Guo T, Zheng JS. Gut microbiota may underlie the predisposition of healthy individuals to COVID-19. MedRxiv. 2020.
  37. Zhao Y, Zeng Y, Zeng D, Wang H, Zhou M, Sun N, Xin J, Khalique A, Rajput DS, Pan K, Shu G, Jing B, Ni X. Probiotics and microRNA: their roles in the host-microbe interactions. Front Microbiol. 2020;11:604462.
  38. Behrouzi A, Ashrafian F, Mazaheri H, Lari A, Nouri M, Riazi Rad F, Hoseini Tavassol Z, Siadat SD. The importance of interaction between MicroRNAs and gut microbiota in several pathways. Microb Pathog. 2020;144:104200. https://doi.org/10.1016/j.micpath.2020.104200
  39. Nakata K, Sugi Y, Narabayashi H, Kobayakawa T, Nakanishi Y, Tsuda M, Hosono A, Kaminogawa S, Hanazawa S, Takahashi K. Commensal microbiota-induced microRNA modulates intestinal epithelial permeability through the small GTPase ARF4. J Biol Chem. 2017;292:15426-33. https://doi.org/10.1074/jbc.M117.788596
  40. Rodriguez-Nogales A, Algieri F, Garrido-Mesa J, Vezza T, Utrilla MP, Chueca N, Garcia F, Olivares M, Rodriguez-Cabezas ME, Galvez J. Differential intestinal anti-inflammatory effects of lactobacillus fermentum and lactobacillus salivarius in DSS mouse colitis: impact on microRNAs expression and microbiota composition. Mol Nutr Food Res. 2017;61:1700144. https://doi.org/10.1002/mnfr.201700144
  41. Macia L, Nanan R, Hosseini-Beheshti E, Grau GE. Host- and microbiota-derived extracellular vesicles, immune function, and disease development. Int J Mol Sci. 2019;21:107. https://doi.org/10.3390/ijms21010107
  42. Li M, Chen WD, Wang YD. The roles of the gut microbiota-miRNA interaction in the host pathophysiology. Mol Med. 2020;26:101.
  43. Cullen BR. MicroRNAs as mediators of viral evasion of the immune system. Nat Immunol. 2013;14:205-10. https://doi.org/10.1038/ni.2537
  44. Aydemir MN, Aydemir HB, Korkmaz EM, Budak M, Cekin N, Pinarbasi E. Computationally predicted SARS-COV-2 encoded microRNAs target NFKB, JAK/STAT and TGFB signaling pathways. Gene Rep. 2021;22:101012. https://doi.org/10.1016/j.genrep.2020.101012
  45. Farshbaf A, Mohtasham N, Zare R, Mohajertehran F, Rezaee SA. Potential therapeutic approaches of microRNAs for COVID-19: challenges and opportunities. J Oral Biol Craniofac Res. 2020;11:132-7.
  46. Saini S, Saini A, Thakur CJ, Kumar V, Gupta RD, Sharma JK. Genome-wide computational prediction of miRNAs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed target genes involved in pulmonary vasculature and antiviral innate immunity. Mol Biol Res Commun. 2020;9:83-91.
  47. Morales L, Oliveros JC, Fernandez-Delgado R, tenOever BR, Enjuanes L, Sola I. SARS-CoV-encoded small RNAs contribute to infection-associated lung pathology. Cell Host Microbe. 2017;21:344-55. https://doi.org/10.1016/j.chom.2017.01.015
  48. Trobaugh DW, Klimstra WB. MicroRNA regulation of RNA virus replication and pathogenesis. Trends Mol Med. 2017;23:80-93. https://doi.org/10.1016/j.molmed.2016.11.003
  49. Fulzele S, Sahay B, Yusufu I, Lee TJ, Sharma A, Kolhe R, Isales CM. COVID-19 virulence in aged patients might be impacted by the host cellular microRNAs abundance/profile. Aging Dis. 2020;11:509-22. https://doi.org/10.14336/ad.2020.0428
  50. Chow JT, Salmena L. Prediction and Analysis of SARS-CoV-2-targeting microRNA in human lung epithelium. Genes (Basel). 2020;11:1002. https://doi.org/10.3390/genes11091002
  51. Arisan ED, Dart A, Grant GH, Arisan S, Cuhadaroglu S, Lange S, Uysal-Onganer P. The prediction of miRNAs in SARS-CoV-2 genomes: hsa-miR databases identify 7 key miRs linked to host responses and virus pathogenicity-related KEGG pathways significant for comorbidities. Viruses. 2020;12:614. https://doi.org/10.3390/v12060614
  52. Li C, Hu X, Li L, Li JH. Differential microRNA expression in the peripheral blood from human patients with COVID-19. J Clin Lab Anal. 2020;34:e23590. https://doi.org/10.1002/jcla.23590
  53. Marchi R, Sugita B, Centa A, Fonseca AS, Bortoletto S, Fiorentin K, Ferreira S, Cavalli LR. The role of microRNAs in modulating SARS-CoV-2 infection in human cells: a systematic review. Infect Genet Evol. 2021;91:104832. https://doi.org/10.1016/j.meegid.2021.104832
  54. Khan AT, Khalid Z, Zahid H, Yousaf MA, Shakoori AR. A computational and bioinformatic analysis of ACE2: an elucidation of its dual role in COVID-19 pathology and finding its associated partners as potential therapeutic targets. J Biomol Struct Dyn. 2020;1-17.
  55. Lu D, Chatterjee S, Xiao K, Riedel I, Wang Y, Foo R, Bar C, Thum T. MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes. J Mol Cell Cardiol. 2020;148:46-9. https://doi.org/10.1016/j.yjmcc.2020.08.017
  56. Nersisyan S, Shkurnikov M, Turchinovich A, Knyazev E, Tonevitsky A. Integrative analysis of miRNA and mRNA sequencing data reveals potential regulatory mechanisms of ACE2 and TMPRSS2. PLoS One. 2020;15:e0235987. https://doi.org/10.1371/journal.pone.0235987
  57. Mukhopadhyay D, Mussa BM. Identification of Novel Hypothalamic MicroRNAs as promising therapeutics for SARS-CoV-2 by regulating ACE2 and TMPRSS2 expression: an in silico analysis. Brain Sci. 2020;10:666. https://doi.org/10.3390/brainsci10100666
  58. Pierce JB, Simion V, Icli B, Perez-Cremades D, Cheng HS, Feinberg MW. Computational analysis of targeting SARS-CoV-2, viral entry proteins ACE2 and TMPRSS2, and interferon genes by host microRNAs. Genes (Basel). 2020;11:1354. https://doi.org/10.3390/genes11111354
  59. Chang CS, Kao CY. Current understanding of the gut microbiota shaping mechanisms. J Biomed Sci. 2019;26:59. https://doi.org/10.1186/s12929-019-0554-5
  60. Masotti A. Interplays between gut microbiota and gene expression regulation by miRNAs. Front Cell Infect Microbiol. 2012;2:137. https://doi.org/10.3389/fcimb.2012.00137
  61. Feng Q, Chen WD, Wang YD. Gut Microbiota: an integral moderator in health and disease. Front Microbiol. 2018;9:151. https://doi.org/10.3389/fmicb.2018.00151
  62. Casciaro M, Di Salvo E, Pioggia G, Gangemi S. Microbiota and microRNAs in lung diseases: mutual influence and role insights. Eur Rev Med Pharmacol Sci. 2020;24:13000-8.
  63. Davoodvandi A, Marzban H, Goleij P, Sahebkar A, Morshedi K, Rezaei S, Mahjoubin-Tehran M, Tarrahimofrad H, Hamblin MR, Mirzaei H. Effects of therapeutic probiotics on modulation of microRNAs. Cell Commun Signal. 2021;19:4. https://doi.org/10.1186/s12964-020-00668-w
  64. Stavropoulou E, Bezirtzoglou E. Probiotics as a weapon in the fight against COVID-19. Front Nutr. 2020;7:614986. https://doi.org/10.3389/fnut.2020.614986
  65. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281-97. https://doi.org/10.1016/S0092-8674(04)00045-5
  66. Shimakami T, Yamane D, Jangra RK, Kempf BJ, Spaniel C, Barton DJ, Lemon SM. Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proc Natl Acad Sci U S A. 2012;109:941-6. https://doi.org/10.1073/pnas.1112263109
  67. Hum C, Loiselle J, Ahmed N, Shaw TA, Toudic C, Pezacki JP. MicroRNA mimics or inhibitors as antiviral therapeutic approaches against COVID-19. Drugs. 2021;81:517-31. https://doi.org/10.1007/s40265-021-01474-5
  68. Sevgin O, Sevgin K. Systematic review of microRNAs in the SARS-CoV-2 infection: are microRNAs potential therapy for COVID-19? J Genet Genome Res. 2021;8:053.
  69. Bana B, Cabreiro F. The microbiome and aging. Annu Rev Genet. 2019;53:239-61. https://doi.org/10.1146/annurev-genet-112618-043650
  70. Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: a review. Clin Immunol. 2020;215:108427. https://doi.org/10.1016/j.clim.2020.108427