Temporal Dynamics of the Resistome of the Intestinal Microbiota of a Healthy Population against the Background of COVID-19

Background. Antibiotics were widely used during the COVID-19 pandemic, which may have led to an increase in the number and diversity of antibiotic resistance genes. Most studies assessing the human resistome during this period were conducted over a short period of time and on different cohorts of people. In this case, the most informative approach is to study the composition of the resistome in people who have and have not recovered from COVID-19, using paired stool samples obtained before and after the pandemic.

The aim of the study was to assess the prevalence of antibiotic resistance genes in the intestinal microbiota of the adult population of Arkhangelsk city before and after the COVID-19 pandemic.

Material and Methods. The study included a random population sample of residents of Arkhangelsk who provided paired stool samples at intervals of five years. The study procedure included surveying and identification of antibiotic resistance genes in stool samples using polymerase chain reaction. Processing of the obtained data was carried out in the R language.

Results. The samples of almost all participants contained genes that cause resistance to macrolides: mefA and ermB. The frequency of glycopeptide resistance genes (vanA and vanB) in post-pandemic samples decreased significantly. There is a trend towards an increase in the number of antibiotic resistance genes among patients hospitalized for COVID-19 compared to outpatients. The proportion of macrolide resistance genes shifted toward an increased relative representation of mefA in post-pandemic samples.

Conclusion. The resistome of study participants did not undergo significant changes during the COVID-19 pandemic, except for a decrease in the prevalence of glycopeptide resistance genes and a change in the ratio of macrolide resistance genes.

1. Sekirov I., Shannon L., Russell L., Caetano М., Antunes, and Finlay, B. B. Gut microbiota in health and disease. Physiol Rev. 2010;90;859–904 doi: 10.1152/physrev.00045.2009.

2. León-Sampedro R., DelaFuente J., Díaz-Agero C., Crellen T., Musicha P., Rodríguez-Beltrán J., San Millán Á. Pervasive transmission of a carbapenem resistance plasmid in the gut microbiota of hospitalized patients. Nat Microbiol, 2021; 6 (5): 606–616. doi: https://doi.org/10.1038/s41564-021-00879-y.

3. Konstantinidis T., Tsigalou C., Karvelas A., Stavropoulou E., Voidarou C., Bezirtzoglou E. Effects of Antibiotics upon the Gut Microbiome: A Review of the Literature. Biomedicines. 2020; 8 (11): 502. doi: 10.3390/biomedicines8110502.

4. Su Q., Liu Q., Zhang L., Xu Z., Liu C., Lu W., Ching J.Y., Li A., Mak J.W.Y., Lui G.C.Y., Ng S.S.S., Chow K.M., Hui D.S., Chan P.K., Chan F.K.L., Ng S.C. Antibiotics and probiotics impact gut antimicrobial resistance gene reservoir in COVID-19 patients. Gut Microbes. 2022; 14: 2128603. doi: 10.1080/19490976.2022.2128603.

5. Fishbein S.R.S., Mahmud B., Dantas G. Antibiotic perturbations to the gut microbiome. Nat Rev Microbiol. 2023; 21; 772–788. doi: 10.1038/s41579-023-00933-y.

6. Kraevoj i dr. Vremennye metodicheskie rekomendatsii. Profilaktika, diagnostika i lechenie novoj koronavirusnoj infektsii (2019-nCoV). versiya 2 (03.02.2020). (in Russian)

7. Karoli N.A., Aparkina A.V., Grigoryeva E.V., Magdeeva N.A., Nikitina N.M., Smirnova N.D., Rebrov A.P. Antibacterial Therapy of Patients With COVID-19 During The Outpatient and Hospital Stages. Antibiot Khimioter = Antibiotics and Chemotherapy. 2022; 67 (1—2): 24–31. doi: https://doi.org/10.37489/0235-2990-2022-67-1-2-24-31.

8. Kang Y., Chen S., Chen Y., Tian L., Wu Q., Zheng M., Li Z. Alterations of fecal antibiotic resistome in COVID-19 patients after empirical antibiotic exposure. Int J Hyg Environmental Health. 2021; 240; 113882. doi: 10.1016/j.ijheh.2021.113882.

9. The R Project for Statistical Computing [Internet] [updated 2023 Oct 313; cited 2023 Nov 23] Available from: https://www.r-project.org/

10. Zhu Q., Jiang S., Du G. Effects of exercise frequency on the gut microbiota in elderly individuals. Microbiologyopen. 2020; 9 (8): e1053. doi: 10.1002/mbo3.1053.

11. Moosavian M., Ghadri H., Samli Z. Molecular detection of vanA and vanB genes among vancomycin-resistant enterococci in ICU-hospitalized patients in Ahvaz in southwest of Iran. Infect Drug Resist. 2018; 11: 2269–2275. doi: 10.2147/IDR.S177886.

12. Seville L.A., Patterson A.J., Scott K.P., Mullany P., Quail M.A., Parkhill J., Ready D., Wilson M., Spratt D., Roberts A.P. Distribution of tetracycline and erythromycin resistance genes among human oral and fecal meta-genomic DNA. Microb Drug Resist. 2009; 15: 159–166. doi: 10.1089/mdr.2009.0916.

13. Klaassen C.H.W., Mouton J.W. Molecular detection of the macrolide efflux gene: to discriminate or not to discriminate between mef(A) and mef(E). Antimicrob Agents Chemother. 2005; 49: 1271–1278. doi: 10.1128/AAC.49.4.1271-1278.2005.

14. Ohashi Y., Fujisawa T. Detection of antibiotic resistance genes in the feces of young adult Japanese. Biosci Microbiota Food Health. 2017; 36: 151–154. doi: 10.12938/bmfh.17-004.

15.