A new look at the alimentary route of tuberculosis transmission using a rabbit model (experimental study)
https://doi.org/10.29413/ABS.2026-11.3.21
Abstract
Background. The increase in the number of cases of generalized tuberculosis infection with intestinal damage, especially in HIV-positive patients, underscores the need for further study of this problem. Tuberculosis is transmitted by airborne droplets; however, there are known cases of intestinal tuberculosis in which infection occurred through the alimentary route. Since such cases are extremely rare, there are likely specific immunological and epidemiological conditions that allow Mycobacterium tuberculosis to penetrate the intestinal wall and develop primary inflammation.
The aim. To study the possibility of an alimentary route of tuberculosis infection in immunocompetent and immunocompromised individuals using a reproducible rabbit model.
Materials and Methods. The experiment involved rabbits, divided into three groups. Animals were orally administered a suspension of a standard laboratory isolate Mycobacterium tuberculosis H37Rv. The first group included immunocompetent rabbits immunosuppressed with infliximab, the second group had animals reinfected against the background of immunodeficiency, and the third group included rabbits with a combination of drug-induced immunosuppression and chemically induced enterocolitis. To assess the results of infection, clinical observation, detection of MTB DNA in feces, skin test with ATR, pathoanatomical, histological and molecular genetic examination of organs were used.
Results. Despite the temporary shedding of MTB DNA in feces (60–70 %), no signs of tuberculous inflammation in the organs were present in animals in groups 1 and 2. In group 3, macroand microscopic signs of tuberculosis were detected in the lungs of 83.3 % of the animals and in the mesenteric/intrathoracic lymph nodes of 58.3 %. At the same time, no specific granulomatous intestinal lesions were found in any of the groups.
Conclusion. The development of tuberculous enterocolitis in rabbits following oral infection is unlikely. The alimentary route of infection can lead to generalized tuberculosis only when two key predisposing factors are present: systemic immunosuppression and previous damage to the intestinal barrier.
About the Authors
M. N. ReshetnikovRussian Federation
Mikhail N. Reshetnikov – Cand. Sc. (Med.), surgeon, leading researcher of the Moscow Research and Clinical Center for Tuberculosis Control of the Moscow Healthcare Department; associate professor of the Department of Phthisiology of the RMACPE.
Stromynka Str., 10, Moscow 107014; Barrikadnaya Str., 2/1-1, Moscow 125993
D. V. Plotkin
Russian Federation
Dmitriy V. Plotkin – Dr. Sc, (Med.), associate professor, surgeon, leading researcher of the Moscow Research and Clinical Center for Tuberculosis Control of the Moscow Healthcare Department; professor of Buyanov General Surgery Department, Institute of Surgery, Pirogov RNRMU.
Stromynka Str., 10, Moscow 107014; Ostrovityanova Str., 1/6, Moscow 117513
T. I. Vinogradova
Russian Federation
Tatyana I. Vinogradova – Dr. Sc. (Med.), professor, chief research officer at the Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; head of the Laboratory of Experimental Tuberculosis.
Ligovskiy Av., 2-4, Saint-Petersburg 191036
M. Z. Dogonadze
Russian Federation
Marine Z. Dogonadze – Cand. Sc. (Biol.), senior research.
Ligovskiy Av., 2-4, Saint-Petersburg 191036
D. A. Ivanova
Russian Federation
Diana A. Ivanova – Dr. Sc. (Med.), scientific secretary of the Moscow Research and Clinical Center for Tuberculosis Control of the Moscow Healthcare Department; professor of the Department of Phthisiology of the Russian Medical Academy of Continuous Professional Education of the Ministry of Healthcare of the RF.
Stromynka Str., 10, Moscow 107014; Barrikadnaya Str., 2/1-1, Moscow 125993
O. N. Zuban
Russian Federation
Oleg N. Zuban – Dr. Sc. (Med.), professor, deputy director for Research and Clinical Activities of the Moscow RCC for Tuberculosis Control of the MHD; professor of the Department of Phthisiology of the Russian Medical Academy of Continuous Professional Education of the Ministry of Healthcare of the Russian Federation.
Stromynka Str., 10, Moscow 107014; Barrikadnaya Str., 2/1-1, Moscow 125993
P. K. Yablonsky
Russian Federation
Petr K. Yablonsky – Dr. Sc. (Med.), professor, director.
Ligovskiy Av., 2-4, Saint-Petersburg 191036
References
1. Hatgoankar K, Hatgaonkar A, Dawande P. Revisiting the Era of Intestinal Tuberculosis: A Case Presenting as Small Bowel Obstruction with Classical Imaging and Histopathological Appearances. Cureus. 2024; 16(1): e51836. doi: 10.7759/cureus.51836
2. Reshetnikov MN, Plotkin DV, Sinitsyn MV, Gafarov UO, Belentseva OV. Surgical complications of abdominal tuberculosis in patients with different immune status. Experimental and Clinical Gastroenterology. 2019; (4): 46-53. (In Russ.). doi: 10.31146/1682-8658-ecg-164-4-46-53
3. Corleis B, Bastian M, Hoffmann D, Beer M, Dorhoi A. Animal models for COVID-19 and tuberculosis. Front Immunol. 2023; 14: 1223260. doi: 10.3389/fimmu.2023.1223260
4. Subbian S, Tsenova L, O’Brien P, Yang G, Kushner NL, Parsons S, et al. Spontaneous latency in a rabbit model of pulmonary tuberculosis. Am J Pathol. 2012; 181(5): 1711-24. doi: 10.1016/j.ajpath.2012.07.019
5. Elkington P, Lerm M, Kapoor N, Mahon R, Pienaar E, Huh D, et al. In Vitro Granuloma Models of Tuberculosis: Potential and Challenges. J Infect Dis. 2019; 219(12): 1858-1866. doi: 10.1093/infdis/jiz020
6. Gómez-Piña JJ. Tuberculosis peritoneal. Med Int Méx. 2018; 34(3): 490-496. doi: 10.24245/mim.v34i3.2171
7. Al-Zanbagi AB, Shariff MK. Gastrointestinal tuberculosis: A systematic review of epidemiology, presentation, diagnosis and treatment. Saudi J Gastroenterol. 2021; 27(5): 261-274. doi: 10.4103/sjg.sjg_148_21
8. Plotkin DV, Reshetnikov MN, Vinogradova TI, Zyuzya YuR, Gafarov UO, Zhuravlev VY, et al. Choosing a model object for reproducing abdominal tuberculosis. Tuberculosis and socially significant diseases. 2021; 9(3): 18-25. (In Russ.). doi: 10.54921/2413-0346-2021-12-3-18-25
9. Rules of work with laboratory rodents and rabbits. Moscow, Standartinform Publ., 2016. (In Russ.).
10. Plotkin DV, Vinogradova TI, Reshetnikov MN, Ariel BM, Zyuzya YR, Zhuravlev VY, et al. Features of the pathogenetic mechanisms of tuberculous peritonitis in an experiment. Bulletin of RSMU. 2021; (4): 20–7. doi: 10.24075/brsmu.2021.036
11. Shekunova EV, Kovaleva MA, Makarova MN, Makarov VG. Dose Selection in Preclinical Studies: Cross-Species Dose Conversion. The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2020; 10(1): 19-28. (In Russ.). doi: 10.30895/1991-2919-2020-10-1-19-28
12. Zhang Q, Lv Hh, Chen A, Liu F, Wu X. Efficacy of infliximab in a rabbit model of osteoarthritis. Connect Tissue Res. 2012; 53(5): 355-358. doi: 10.3109/03008207.2012.661001
13. Henriksen ML, Teisner A, Kjeldsen J, Kalliokoski O, Hau J, Hansen SW. The Effect of Induced Antibodies with Respect to Neutralization, Clearance Rate and Functional Activity in a Rabbit/Infliximab Model. In Vivo. 2016; 30(5): 557-565.
14. Leonardi I, Nicholls F, Atrott K, Cee A, Tewes B, Greinwald R, et al. Oral administration of dextran sodium sulphate induces a caecum-localized colitis in rabbits. Int J Exp Pathol. 2015; 96(3): 151-62. doi: 10.1111/iep.12117
15. Reshetnikov MN, Vinogradova TI, Zyuzya YuR, Plotkin DV, Volkov AA, Dogonadze MZ, et al. Choosing the optimal concentration of dextran sulfate sodium for reproducing chemically induced colitis in rabbits. Experimental and Clinical Gastroenterology. 2023; (9): 125-130. (In Russ.). doi: 10.31146/1682-8658-ecg-217-9-125-130
16. Long R, Divangahi M, Schwartzman K. Chapter 2: Transmission and pathogenesis of tuberculosis. Canadian Journal of Respiratory, Critical Care, and Sleep Medicine. 2022; 6(sup 1): 22–32. doi: 10.1080/24745332.2022.2035540
17. Perelman MI. Phthisiology. National Leadership. Moscow: Publishing house GЕOTAR-Media, 2007, 512 p. (National Guidelines Series). (In Russ.).
18. Tobin EH, Khatri AM. Abdominal Tuberculosis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. URL: https://www.statpearls.com/point-ofcare/30658. [date of access: November 16, 2025].
19. Villemin JA. Études sur la tuberculose. Paris: Baillière, 1868: 241 p. (In French).
20. McConkey M, Smith DT. The relation of vitamin C deficiency to intestinal tuberculosis in the guinea pig. J Exp Med. 1933; 58(4): 503-12. doi: 10.1084/jem.58.4.503
21. Clark S, Hall Y, Williams A. Animal models of tuberculosis: Guinea pigs. Cold Spring Harb Perspect Med. 2014; 5(5): a018572. doi: 10.1101/cshperspect.a018572
22. Larenas-Muñoz F, Ruedas-Torres I, Hunter L, Bird A, Agulló-Ros I, Winsbury R, et al. Characterisation and development of histopathological lesions in a guinea pig model of Mycobacterium tuberculosis infection. Front Vet Sci. 2023; 10: 1264200. doi: 10.3389/fvets.2023.1264200
23. Gao J, Guo M, Teng L, Bao R, Xian Q, Wang X, et al. Guinea pig infected with Mycobacterium tuberculosis via oral consumption. Journal of Applied Animal Research. 2018; 46(1): 1323–1328. doi: 10.1080/09712119.2018.1505622
24. Shtefko VG. Experimental intestinal tuberculosis and the method of its production. Problems of tuberculosis. 1941; 5: 15-20 (In Russ.).
25. Belei O, Basaca DG, Olariu L, Pantea M, Bozgan D, Nanu A, et al. The Interaction between Stress and Inflammatory Bowel Disease in Pediatric and Adult Patients. J Clin Med. 2024; 13(5): 1361. doi: 10.3390/jcm13051361
26. Casto-Rebollo C, Argente MJ, García ML, Blasco A, Ibáñez-Escriche N. Effect of environmental variance-based resilience selection on the gut metabolome of rabbits. Genet Sel Evol. 2023; 55(1): 15. doi: 10.1186/s12711-023-00791-5
27. Chassaing B, Kumar M, Baker MT, Singh V, Vijay-Kumar M. Mammalian gut immunity. Biomed J. 2014; 37(5): 246-58. doi: 10.4103/2319-4170.130922
Review
For citations:
Reshetnikov M.N., Plotkin D.V., Vinogradova T.I., Dogonadze M.Z., Ivanova D.A., Zuban O.N., Yablonsky P.K. A new look at the alimentary route of tuberculosis transmission using a rabbit model (experimental study). Acta Biomedica Scientifica. 2026;11(3):171-181. https://doi.org/10.29413/ABS.2026-11.3.21
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