Gut microbiota: A protective mechanism against tuberculosis in children with household contacts in a TB-endemic environment
Keywords:
Tuberculosis, gut microbiota, childrenAbstract
Background and aim: The gut-lung axis has contributed to the impairment of pulmonary infectious diseases. Gut microbiota appears to play a crucial role in modulating host immunity against tuberculosis (TB) infection in children. We examined the gut microbiota in children with tuberculosis and those who were in close contact and residing in the same household.
Methods: A cross-sectional study was conducted involving patients aged from 1 month to 18 years who were diagnosed with bacterial confirmation of tuberculosis. Contact investigations were conducted for all patients. The sibling residing in the same household underwent screening for tuberculosis using a tuberculin test. Fecal samples were obtained from two groups upon admission. Next-generation sequencing was utilized to analyze the 16sRNA of the samples.
Results: This study showed a notable decrease in the relative abundance of the phylum Bacillota was observed in children with TB disease compared to those exposed to TB. The diversity of microbiota is altered, as indicated by a decrease in both the Shannon index and the Simpson's index in children with TB disease.
Conclusions: The gut microbiota in children with TB disease exhibited distinct differences compared to those exposed to TB, particularly in terms of the relative abundance of bacteria. This work will provide an understanding of gut microbiota influence on control mechanisms of TB infection in children.
References
References
1. Comberiati P, Di Cicco M, Paravati F, Pelosi U, Di Gangi A, Arasi S, et al. The role of gut and lung microbiota in susceptibility to tuberculosis. Int J Environ Res Public Health. 2021 Nov 21;18(22):12220. doi: 10.3390/ijerph182212220
2. Wang Y, Deng Y, Lie N, Chen Y, Jiang Y, Teng Z, et al. Alteration in the gut microbiome of individuals with tuberculosis of different disease states. Frontiers in Cellular and Infection Microbiology. 2022. 12:836987. doi: 10.3389/fcimb.2022.836987.
3. WHO. Global tuberculosis report. WHO. 2024. Citated at https://www.who.int/teams/global-programme-on-tuberculosis-and-lung-health/tb-reports/global-tuberculosis-report-2024.
4. Laghari M, Sulaiman SAS, Khan AH, Talpur BA, Bhatti Z, Memon N. Contact screening and risk factors for TB among the household contact of children with active TB: A way to find source case and new TB cases. BMC Public Health. 2019 Sept 18;19(1).1274 doi: 10.1186/s12889-019-7597-0
5. Carvalho I, Goletti D, Manga S, Silva DR, Manissero D, Migliori G. Managing latent tuberculosis infection and tuberculosis in children. Pulmonology. 2018 Mar-Apr; 24(2):106–114. doi: 10.1016/j.rppnen.2017.10.007.
6. Hamada Y, Glaziou P, Sismanidis C, Getahun H. Prevention of tuberculosis in household members : estimates of children eligible for treatment. Bull World Health Organ. 2019 August. 97(8):534-547D. doi:10.2471/BLT.18.218651
7. Eribo OA, Plessis N, Ozturk M, Guler R, Walzl G, Chegou NN. The gut microbiome in tuberculosis susceptibility and treatment response: guilty or not guilty?. Cell Mol Life Sci. 2020 Apr;77(8):1497-1509. doi: 10.1007/s00018-019-03370-4.
8. Liu W, Zhu Y, Liao Q, Wang Z, Wan C. Characterization of gut microbiota in children with pulmonary tuberculosis. BMC Pediatrics. 2019.19:445. doi : 10.1186/s12887-019-1782-2.
9. Han M, Wang X, Zhang J, Su L, Ishaq HM, Li D, et al. Gut bacterial and fungal dysbiosis in tuberculosis patients. BMC Microbiology. 2024. 24:141. doi : 10.1186/s12866-024-03275-8.
10. Barbosa-Amezcua M, Galeana-Cadena D, Alvarado-Peña N, Silva-Herzog E. The Microbiome as Part of the Contemporary View of Tuberculosis Disease. Pathogens. 2022 May 16. 11(5):584. doi : 10.3390/pathogens11050584
11. Yu Z, Shen X, Wang A, Hu C, Chen J. The gut microbiome: A line of defense against tuberculosis development. Front. Cell. Infect. Microbiol. 2023 April 18; 13:1149679. doi.org/10.3389/fcimb.2023.1149679
12. Yang F, Yang Y, Chen L, Zhang Z, Liu L, Zhang C, et al. The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA. Gut Microbes. 2022 Jan-Dec;14(1):2029997. doi: 10.1080/19490976.2022.2029997.
13. Gupta N, Kumar R, Agrawal B. New players in immunity to tuberculosis: the host microbiome, lung epithelium, and innate immune cells. Front. Immunol. 2018 April 10. 9:709. doi.org/10.3389/fimmu.2018.00709
14. Kleinnijenhuis J, Oosting M, Joosten L, Netea M, Crevel R. Innate Immune Recognition of Mycobacterium tuberculosis. Clin Dev Immunol. 2011 April 7. 2011:405310. doi: 10.1155/2011/405310
15. Osei Sekyere J, Maningi NE, Fourie PB. Mycobacterium tuberculosis, antimicrobials, immunity, and lung-gut microbiota crosstalk: current updates and emerging advances. Ann N Y Acad Sci. 2020 may; 1467(1), 21–47. doi: 10.1111/nyas.14300.
16. Hand TW. The role of the microbiota in shaping infectious immunity. Trends Immunol. 2016 Oct;37(10):647–58. doi: 10.1016/j.it.2016.08.007
17. Shukla SD, Budden KF, Neal R, Hansbro PM. Microbiome effects on immunity, health and disease in the lung. Clin Transl Immunology. 2017 Mar 10; 6(3):e133. doi: 10.1038/cti.2017.6
18. O’Dwyer DN, Dickson RP, Moore BB. The lung microbiome, immunity, and the pathogenesis of chronic lung disease. J Immunol. 2016 Jun 15. 196(12):4839– 47. doi : 10.4049/jimmunol.1600279
19. Budden KF, Gellatly SL, Wood DL, Cooper MA, Morrison M, Hugenholtz P, et al. Emerging pathogenic links between microbiota and the gut-lung axis. Nat Rev Microbiol. 2017 Jan. 15(1):55–63. doi: 10.1038/nrmicro.2016.142.
20. Dickson RP, Erb-Downward JR, Huffnagle GB. The role of the bacterial microbiome in lung disease. Expert Rev Respir Med. 2013 Jun. 7(3):245– 57. doi: 10.1586/ers.13.24
21. Namasivayam S, Sher A, Glickman MS, Wipperman MF. The Microbiome and Tuberculosis: Early Evidence for Cross Talk. mBio. 2018 Sep 18; 9(5):e01420-18. doi: 10.1128/mBio.01420-18
22. Ronan V, Yeasin R, Claud EC. Childhood development and the microbiome: The intestinal microbiota in maintenance of health and development of disease during childhood development. Gastroenterology. 2021 Jan. 160(2):495-506. doi: 10.1053/j.gastro.2020.08.065.
23. Ma J, Li Z, Zhang W, Zhang C, Zhang Y, Mei H, et al. Comparison of gut microbiota in exclusively breast-fed and formula-fed babies: a study of 91 term infants. Sci Rep. 2020 Sep 25; 10(1):15792. doi: 10.1038/s41598-020-72635-x
24. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017 may 16. 474(11): 1823–1836. doi: 10.1042/BCJ20160510
25. Tanaka M, Nakayama J. Development of the gut microbiota in infancy and its impact on health in later life. Allergol Int. 2017 Oct; 66(4):515–522. doi: 10.1016/j.alit.2017.07.010.
26. Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cell Mol Life Sci. 2019 Feb; 76(3): 473–493. doi: 10.1007/s00018-018-2943-4.
27. Wipperman MF, Fitzgerald DW, Juste MAJ, Taur Y, Namasivayam S, Sher A, et al. Antibiotic treatment for Tuberculosis induces a profound dysbiosis of the microbiome that persists long after therapy is completed. Sci Rep. 2017 Sep 7; 7(1): 10767. doi: 10.1038/s41598-017-10346-6.
28. Luo M, LiuY, Wu P, Luo DX, Sun Q, Zheng H, et al. Alternation of gut microbiota in patients with pulmonary tuberculosis. Front Physiol. 2017 Nov 17. 8:822. doi: 10.3389/fphys.2017.00822.
29. Shah T, Shah Z, Baloch Z, Cui X. The role of microbiota in respiratory health and diseases, particularly in tuberculosis. Biomedicine and Pharmacotherapy. 2021 Nov. 143, 112108. https://doi.org/10.1016/j.biopha.2021.112108
30. Hu Y, Yang Q, Liu B, Dong J, Sun L, Zhu Y, et al. Gut microbiota associated with pulmonary tuberculosis and dysbiosis caused by anti-tuberculosis drugs. J Infect. 2019 Apr; 78(4); 317–322. doi: 10.1016/j.jinf.2018.08.006
31. Mori G, Morrison M, Blumenthal A. Microbiome-immune interactions in tuberculosis. PLoS Pathogens. 2021 Apr 15. 17. doi.org/10.1371/journal.ppat.1009377
32. Nguyen M, Ahn P, Dawi J, Gargaloyan A, Kiriaki A, Shou T, et al. The Interplay between Mycobacterium tuberculosis and Human Microbiome. Clin Pract. 2024 Jan 24; 14(1):198-213. doi: 10.3390/clinpract14010017
33. Khaliq A, Ravindran R, Afzal S, Jena PK, Akhtar MW, Ambreen A, et al. Gut microbiome dysbiosis and correlation with blood biomarkers in active- tuberculosis in endemic setting. PLoS One. 2021 Jan 22;16(1):e0245534. doi: 10.1371/journal.pone.0245534
34. Winglee K, Eloefadrosh E, Gupta S, Guo H, Fraser C, Bishai W. Aerosol mycobacterium tuberculosis infection causes rapid loss of diversity in gut microbiota. PLoS One. 2014 may 12. 9(5):e97048. doi.org/10.1371/journal.pone.0097048
35. Namasivayam S, Maiga M, Yuan W, Thovarai V, Costa DL, Mittereder LR, Wipperman MF, Glickman MS, Dzutsev A, Trinchieri G. Longitudinal profiling reveals a persistent intestinal dysbiosis triggered by conventional anti- tuberculosis therapy. Microbiome. 2017 July 7;5(1):71. doi: 10.1186/s40168-017-0286-2.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Rika Hapsari, Anang Endaryanto, Ni Made Mertaniasih, Retno Asih Setyoningrum, Arda Pratama Putra Chafid, Azizah Hamida

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.