The Impact of Chemotherapy for Drug-Resistant Respiratory Tuberculosis on the Composition of Fecal Microbiota in Children

The objective: to study the species and quantitative composition of fecal microbiota in children undergoing chemotherapy for drug-resistant respiratory tuberculosis.

Subjects and Methods. The study included 17 children from 2 to 12 years old with respiratory tuberculosis who received treatment for drug-resistant respiratory tuberculosis from 2022 to 2024 at Central Tuberculosis Research Institute. Fecal microbiota was tested by real-time PCR using the ENTEROFLOR® Children reagent kit at the following time points: before the start of chemotherapy, after 2 and 4 months of chemotherapy.

Results. The most pronounced disturbances in the intestinal microbiocenosis among representatives of normobiota were noted after 2 months of chemotherapy; by 4 months, those parameters did not deteriorate either in quantitative terms or frequency of deviations from reference values: for representatives of the phylum Actinomycetota (Actinobacteria) – in Bifidobacterium spp. and Coriobacteriia, for representatives of the phylum Bacteroidota (Bacteroidetes) – in Butyricimonas spp., Parabacteroides spp., Prevotella spp. Changes in the composition of normobiota were associated with the elevated proportion of opportunistic microbiota by 2 months and persistence of these values by 4 months of chemotherapy. Representatives of pathogenic microbiota, which were not present before chemotherapy, appeared by 2 months of chemotherapy with the following frequency: Streptococcus agalactiae – in 35.3% of cases, Clostridioides difficile, with the toxigenic genes cdtA and cdtB – in 58.9%, and increasing to 71.5% by 4 months of chemotherapy.

Conclusion. Treatment with chemotherapy regimens for drug-resistant tuberculosis has a statistically significant negative impact on intestinal microbiota in children: the proportion of normobiota decreases, the proportion of opportunistic microbiota increases, and pathogenic microbiota develops.

1. Ardatskaya M.D. The role of low molecular weight metabolites of the intestinal microbiota in the pathogenesis, diagnosis and prevention of colorectal cancer. Experimental and Clinical Gastroenterology, 2017, vol. 139, no. 3, pp. 13-21. (In Russ.)

2. Tuberkulez u detey. Klinicheskie rekomendatsii. [Tuberculosis in children. Guidelines]. RSP Publ., 2024. Available: https://cr.minzdrav.gov.ru/view-cr/507_3. Accessed January 7, 2025

3. Usenko D.V. Antibiotic-induced changes in the microbiota of the gastrointestinal tract and their correction. RMJ, 2018, vol. 26, no. 2 (II), pp. 96-99. (In Russ.)

4. Chunxi L., Haiyue L., Yanxia L., Jianbing P., Jin S. The gut microbiota and respiratory diseases: new evidence. J. Immunol. Res., 2020, no. 1, pp. 2340670. https://doi.org/10.1155/2020/2340670

5. Edlund C., Beyer G., Hiemer-Bau M., Ziege S., Lode H., Nord C.E. Comparative effects of moxifloxacin and clarithromycin on the normal intestinal microflora. Scand. J. Infect. Dis., 2000, vol. 32, no. 1, pp. 81-85. https://doi.org/10.1080/00365540050164272

6. Lode H., Von der Hоh N., Ziege S. et al. Ecological effects of linezolid versus amoxicillin/clavulanic acid on the normal intestinal microflora. Scand. J. Infect. Dis., 2001, vol. 33, no. 12, pp. 899-903.

7. Lynch S. The human intestinal microbiome in health and disease. The New England Journal of Medicine, 2016, vol. 375, no. 24, pp. 2369-2379. https://doi.org/10.1056/NEJMra1600266

8. Queen J., Zhang J., Sears C.L. Oral antibiotic use and chronic disease: long-term health impact beyond antimicrobial resistance and Clostridioides difficile. Gut Microbes, 2020, vol. 11, no. 4, pp. 1092-1103. https://doi.org/10.1080/19490976.2019.1706425

9. Ramirez J., Guarner F., Bustos Fernandez L., Maruy A., Sdepanian V.L., Cohen H. Antibiotics as major disruptors of gut microbiota. Front. Cell. Infect. Microbiol., 2020, vol. 24, no. 10, pp. 572912. https://doi.org/10.3389/fcimb.2020.572912

10. Rui L., Zhengsheng M., Xujun Y., Tao Zuo H. Gut microbiome and liver diseases: from correlation to causation. Microorganisms, 2021, vol. 9, no. 5, pp. 1017. https://doi.org/10.3390/microorganisms9051017

11. Torun A. Intestinal microbiota in common chronic inflammatory disorders affecting children. Front Immunol., 2021, no. 12, pp. 642166. https://doi.org/10.3389/fimmu.2021.642166

12. Xing R., Liu H., Qi X., Pan L. Measuring the process and rate of exogenous DNA degradation during digestion in mice. Sci. Rep., 2022, vol. 12, no. 1, pp. 6463. https://doi.org/10.1038/s41598-022-10340-7