ORIGINAL RESEARCH

Gut microbiota alterations and their relationship to the disease severity and some cytokine profile indicators in patients with COVID-19

Gumenyuk LN, Golod MV, Silaeva NV, Sorokina LE, Ilyasov SS, Androschyuk NA, Krivoshapko OR, Velilyaev AM, Asanova LN
About authors

V.I. Vernadsky Crimean Federal University, Simferopol, Russia

Correspondence should be addressed: Leya E. Sorokina
Bulvar Lenina, 5/7, Simferopol, 295006, Republic of Crimea; ur.liam@anikoros.ayel

About paper

Author contribution: Gumenyuk LN, Sorokina LE — significant contribution to the study concept and design; Golod MV, Silaeva NV, Androschyuk NA — data acquisition, analysis, and interpretation; Ilyasov SS — statistical data processing; Krivoshapko OR, Velilyaev AM, Asanova LN — manuscript writing.

Compliance with ethical standards: the study was approved by the Ethics Committee of the S.I. Georgievsky Medical Academy, V.I. Vernadsky Crimean Federal University (protocol № 11 dated November 23, 2021), planned and conducted in accordance with the Declaration of Helsinki. The informed consent was obtained from all study participants.

Received: 2022-01-18 Accepted: 2022-02-02 Published online: 2022-02-19
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  1. Statement on the second meeting of the International Health Regulations Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV). World Health Organization (WHO), 2020. Available from: https://www.who.int/news-room/detail/3001-2020-statement-on-the-second-meeting-of-the-internationalhealth-regulations-(2005)-emergency-committee-regarding-theoutbreak-of-novel-coronavirus-(2019-ncov) (assessed Dec 15, 2021).
  2. Tao W, Zhang G, Wang X, et al. Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL18. Med Microecol. 2020; 5: 100023. DOI:10.1016/j. medmic.2020.100023.
  3. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020; 20 (6): 363–74. DOI: 10.1038/s41577-0200311-8.
  4. Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev. 2020; 54: 62–75. DOI: 10.1016/j.cytogfr.2020.06.001.
  5. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395: 1054–62. DOI: 10.1016/S0140-6736(20)30566-3.
  6. Lamers MM, Beumer J, van der Vaart J, et al. SARS-CoV-2 productively infects human gut enterocytes. Science. 2020; 369 (6499): 50–54. DOI: 10.1126/science.abc1669.
  7. Zuo T, Zhang F, Lui GCY, et al. Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. Gastroenterology. 2020; 159 (3): 944–55.e8. DOI:10.1053/j. gastro.2020.05.048.
  8. Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020; 382 (18): 1708–20. DOI: 10.1056/NEJMoa2002032.
  9. Chan KH, Poon LL, Cheng VC, et al. Detection of SARS coronavirus in patients with suspected SARS. Emerg Infect Dis. 2004; 10 (2): 294–9. DOI: 10.3201/eid1002.030610.
  10. Wu HJ, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes. 2012; 3 (1): 4–14. DOI: 10.4161/ gmic.19320.
  11. Gu S, Chen Y, Wu Z, et al. Alterations of the Gut Microbiota in Patients With Coronavirus Disease 2019 or H1N1 Influenza. Clin Infect Dis. 2020; 71 (10): 2669–78. DOI: 10.1093/cid/ciaa709.
  12. Zuo T, Liu Q, Zhang F, et al. Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut. 2021; 70 (2): 276–84. DOI: 10.1136/ gutjnl-2020-322294.
  13. Mareev VYu, Begrambekova YuL, Mareev YuV. Kak ocenivat' rezul'taty lechenija bol'nyh s novoj koronavirusnoj infekciej (COVID-19)? Shkala Ocenki Klinicheskogo Sostojanija (ShOKS– KOVID). Kardiologija. 2020; 60 (11): 35–41. Russian.
  14. Mitra S, Forster-Fromme K, Damms-Machado A, et al. Analysis of the intestinal microbiota using SOLiD16S rRNA gene sequencing and SOLiD shotgun sequencing. BMC Genomics. 2013; 14 (5): 16.
  15. Caporaso JG, Kuczynski J, Stombaugh J, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010; 7 (5): 335–6. DOI: 10.1038/ nmeth.f.303.
  16. DeSantis, TZ, Hugenholtz P, Larsen N. Greengenes, a chimerachecked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol. 2006; 72: 5069–72.
  17. Ritari J, Salojärvi J, Lahti L, de Vos WM. Improved taxonomic assignment of human intestinal 16S rRNA sequences by a dedicated reference database. BMC Genomics. 2015; 16 (1): 1056. DOI: 10.1186/s12864-015-2265-y.
  18. Gaibani P, D'Amico F, Bartoletti M, et al. The Gut Microbiota of Critically Ill Patients With COVID-19. Front Cell Infect Microbiol. 2021; 11: 670424. DOI: 10.3389/fcimb.2021.670424.
  19. Gilmore MS, Clewell DB, Ike Y, Shankar N, eds. Enterococci: From Commensals to Leading Causes of Drug Resistant Infection. Boston: Massachusetts Eye and Ear Infirmary, 2014.
  20. Tamburini FB, Andermann TM, Tkachenko E, Senchyna F, Banaei N, Bhatt AS. Precision identification of diverse bloodstream pathogens in the gut microbiome. Nat Med. 2018; 24 (12): 1809– 14. DOI: 10.1038/s41591-018-0202-8.
  21. Yeoh YK, Zuo T, Lui GC, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021; 70 (4): 698–06. DOI: 10.1136/ gutjnl-2020-323020.
  22. Danilenko VN, Devyatkin AV, Marsova MV, et al Common in– ammatory mechanisms in COVID-19 and Parkinson’s diseases: the role of microbiome, pharmabiotics and postbiotics in their prevention. Journal of Inflammation Research. 2021; 14, 6349–81. DOI: 10.2147/JIR.S333887.
  23. Poluektova E, Yunes R, Danilenko V. The Putative Antidepressant Mechanisms of Probiotic Bacteria: Relevant Genes and Proteins. Nutrients. 2021; 13 (5): 1591. DOI: 10.3390/nu13051591.
  24. West CE, Renz H, Jenmalm MC, et al. The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies. J Allergy Clin Immunol. 2015; 135 (1): 3–14. DOI: 10.1016/j.jaci.2014.11.012.
  25. Sun Z, Song ZG, Liu C, et al. Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients. BMC Med. 2022; 24: 20. DOI: 10.1186/ s12916-021-02212-0.
  26. Buharin OV, Chajnikova IN, Ivanova EV, i dr. Immunoreguljatornyj profil' mikrosimbiontov kishechnogo biotopa cheloveka. Zhurnal mikrobiologii, jepidemiologii i immunobiologii. 2018; 4: 42–51. Russian.
  27. Hursitoglu M, Isıksacan N, Erismis B, et al. In-vitro cytokine production and nasopharyngeal microbiota composition in the early stage of COVID-19 infection. Cytokine. 2022; 149: 155757. DOI: 10.1016/j.cyto.2021.155757.
  28. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA. 2008; 105 (43): 16731–6. DOI: 10.1073/pnas.0804812105.
  29. Zhang M, Qiu X, Zhang H, et al. Faecalibacterium prausnitzii inhibits interleukin-17 to ameliorate colorectal colitis in rats. PLoS One. 2014; 9 (10): e109146. DOI: 10.1371/journal.pone.0109146.
  30. Zhou L, Zhang M, Wang Y, et al. Faecalibacterium prausnitzii Produces Butyrate to Maintain Th17/Treg Balance and to Ameliorate Colorectal Colitis by Inhibiting Histone Deacetylase 1. Inflamm Bowel Dis. 2018; 24 (9): 1926–40. DOI: 10.1093/ibd/izy182.
  31. van der Lelie D, Taghavi S. COVID-19 and the Gut Microbiome: More than a Gut Feeling. mSystems. 2020; 5 (4): e00453-20. DOI: 10.1128/mSystems.00453-20.
  32. Li L, Zhong Q. Correlation of intestinal microflora with cytokines and Toll-like receptors expression in patients with ulcerative colitis. Infect Dis Inf. 2017; 30 (6): 361–4. DOI: 10.3969/j.issn.10078134.2017.06.012.
  33. Lu J, Ma SS, Zhang WY, Duan JP. Changes in peripheral blood inflammatory factors (TNFα and IL6) and intestinal flora in AIDS and HIV-positive individuals. J Zhejiang Univ Sci B. 2019; 20 (10): 793–802. DOI: 10.1631/jzus.B1900075.