Спорообразующие пробиотики: что мы знаем о них?

Введение. Кишечная микрофлора имеет ключевое значение в поддержании здоровья организма, обмена веществ, усвоения питательных компонентов и регуляции иммунитета. На фоне различных заболеваний происходит нарушение состава микрофлоры и запуск формирования целого ряда органических и функциональных заболеваний. Пробиотические препараты могут способствовать восстановлению микробного баланса кишечника и поддержанию гомеостаза. Виды рода Bacillus и родственных родов (Alkalihalobacillus и Heyndrickxia) на сегодняшний день хорошо изучены и применяются в практике в качестве пробиотиков благодаря их способности образовывать эндоспоры, которые обеспечивают высокую устойчивость к неблагоприятным условиям.

Результаты. Многие полезные свойства спорообразующих пробиотиков, такие как адгезия к стенке кишечника, размножение в кишечнике, устойчивость к экстремальным условиям, иммуномодулирующее действие, выработка биологически активных и антимикробных соединений, рассмотрены в представленной обзорной статье. Рассматривается возможность множественных положительных клинических эффектов Bacillus clausii для профилактики и лечения антибиотикоассоциированной диареи у взрослых и детей, эрадикационнной терапии инфекции Helicobacter pylori, ротавирусной инфекции у детей, синдрома раздраженного кишечника у детей и взрослых, рецидивирующей афтозной язвы и кандидоза полости рта у взрослых, респираторных инфекций у детей, а также при лечении псориаза и функциональной диспепсии.

1. Кoren O., Collado M. C., Chassaing B., et al. Microbial metabolites at the front line: Orchestrating gastrointestinal and systemic barrier immunity across the lifespan. Cell Rep. 2026; 45 (6): 117556.

2. Ray S., Shankaran P. Nutrition and the gut microbiome: a symbiotic dialogue influencing health and disease. Front Nutr. 2026; 13: 1761992.

3. Yu W., Sun S., Fu Q. The role of short-chain fatty acid in metabolic syndrome and its complications: focusing on immunity and inflammation. Front Immunol. 2025; 16: 1519925.

4. Chen Y., Peng Y., Niu Q., et al. The impact of probiotics therapy on cognitive and metabolic characteristics in patients with cognitive impairment: An umbrella review of meta-analysis of randomized controlled trials. Eur J Pharmacol. 2025; 994: 177326.

5. Elisashvili V., Kachlishvili E., Chikindas M. L. Recent Advances in the Physiology of Spore Formation for Bacillus Probiotic Production. Probiotics Antimicrob Proteins. 2019; 11 (3): 731-747.

6. Bambridge N. B., Lu Y., Schirra H. J., еt al. Marine-Derived Bacillus and Their Potential as Probiotics. Int J Mol Sci. 2026; 27 (10): 4352.

7. Luhur J., Chan H., Kachappilly B., et al. A dynamic, ring-forming MucB / RseB-like protein influences spore shape in Bacillus subtilis. PLoS Genet. 2020; 16 (12): e1009246.

8. Ye F., Suryadevara D., Bannon W. J. 4th. Effects of sporulation times in liquid or on plates on Bacillus subtilis spore resistance, germination, inner membrane f luidity and permeability, and core contents. J Bacteriol. 2025; 207 (12): e0038925.

9. Duc L. H., Hong H. A., Barbosa T. M., et al. Characterization of Bacillus probiotics available for human use. Appl. Environ. Microbiol. 2004; 70: 2161-2171.

10. Ghelardi E., Abreu. Y. Abreu A. T. Current Progress and Future Perspectives on the Use of Bacillus clausii. Microorganisms. 2022; 10 (6): 1246.

11. Nachin L., Nannmark U., Nystrom T. Differential roles of the universal stress proteins of Escherichia coli in oxidative stress resistance, adhesion, and motility. J. Bacteriol. 2005; 187: 6265-6272.

12. Khatri I., Sharma G., Subramanian S. Composite genome sequence of Bacillus clausii, a probiotic commercially available as Enterogermina (R), and insights into its probiotic properties. BMC Microbiol. 2019; 19: 307.

13. Cutting S. M. Bacillus probiotics. Food Microbiol. 2011; 28: 214-220.

14. Boyte M. E., Benkowski A., Pane M., et al. Probiotic and postbiotic analytical methods: a perspective of available enumeration techniques. Front Microbiol. 2023; 14: 1304621.

15. Gupta P., Caldbeck R., Walters R. C., еt al. Early activation of bioenergetic metabolism powers bacterial spore germination. Proc Natl Acad Sci USA. 2025; 122 (52): e2510996122.

16. Swarge B., Nafid C., Vischer N., et al. Investigating Synthesis of the MalS Malic Enzyme during Bacillus subtilis Spore Germination and Outgrowth and the Influence of Spore Maturation and Sporulation Conditions. mSphere. 2020; 5 (4): e00464-20.

17. Bernardeau M., Lehtinen M. J., Forssten S. D., et al. Importance of the gastrointestinal life cycle of Bacillus for probiotic functionality. J. Food Sci. Technol. 2017; 54: 2570-2584.

18. Mazzantini D., Calvigioni M., Celandroni F., et al. In vitro assessment of probiotic attributes for strains contained in commercial formulations. Sci. Rep. 2022; 12: 21640.

19. Ghelardi E., Celandroni F., Salvetti S., et al. Survival and persistence of Bacillus clausii in the human gastrointestinal tract following oral administration as spore-based probiotic formulation. J. Appl. Microbiol. 2015; 119: 552-559.

20. Mazzantini D., Calvigioni M., Celandroni F., et al. In vitro analysis of an Alkalihalobacillus clausii spore-based probiotic formulation clarifies the mechanisms underlying its beneficial properties. Biomolecules. 2025; 15: 1294.

21. Khatri A. M., Rai S., Shank C., et al. A tale of caution: Prolonged Bacillus clausii bacteraemia after probiotic use in an immunocompetent child. Access Microbiol. 2021; 3: 000205.

22. Corredor-Rengifo D., Tello-Cajiao M. E., Garcia-Molina F. A., et al. Bacillus clausii Bacteremia Following Probiotic Use: A Report of Two Cases. Cureus. 2024; 16: e57853.

23. Joshi S., Udani S., Sen S., et al. Bacillus Clausii Septicemia in a Pediatric Patient After TreatmentWith Probiotics. Pediatr. Infect. Dis. J. 2019; 38: e228-e230.

24. Munoz M., Castano G. E., Esquivel Suman R., et al. Septicemia due to Bacillus clausii after the use of probiotics. A complication to keep in mind. Septicemia por Bacillus clausii posterior al uso de probioticos. Una complicacion para tener presente. Andes Pediatr. Rev. Chil. Pediatr. 2023; 94: 379-385.

25. Mazzantini D., Calvigioni M., Celandroni F., et al. Spotlight on the Compositional Quality of Probiotic Formulations MarketedWorldwide. Front. Microbiol. 2021; 12: 693973.

26. Çelebi Çongur E., Dalgıç N. A revision of probiotic safety in children. J Pediatr Inf. 2023; 17 (2): e73-e78.

27. Nguyen H. A., Tran P. T., Dam H. T., et al. Whole genome sequence analysis of Bacillus amyloliquefaciens strain S2.5 as a potential probiotic for feed supplement in livestock production. J Genet Eng Biotechnol. 2024; 22 (3): 100404.

28. Koopman N., Remijas L., Seppen J., et al. Mechanisms and applications of bacterial sporulation and germination in the intestine. Int. J. Mol. Sci. 2022; 23: 3405.

29. Pan I., Issac P. K., Rahman M. M., et al. Gut-Brain Axis a Key Player to Control Gut Dysbiosis in Neurological Diseases. Mol Neurobiol. 2024; 61 (12): 9873-9891.

30. Fusco W., Lorenzo M. B., Cintoni M., et al. Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota. Nutrients. 2023; 15 (9): 2211.

31. Safronova L. S., Skorochod I. A., Ilyash V. M. Antioxidant and Antiradical Properties of Probiotic Strains Bacillus amyloliquefaciens ssp. plantarum. Probiotics Antimicrob Proteins. 2021; 13 (6): 1585-1597.

32. Nicolas G. M., Ma S. Effects of Heyndrickxia coagulans probiotics in the human gut microbiota and their health implications: A review. Food Wellness. 2025; 1: 100003.

33. Kazan D., Bal H., Denizci A. A., et al. Studies on alkaline serine protease produced by Bacillus clausii GMBE 22. Prep. Biochem. Biotechnol. 2009; 39: 289-307.

34. Lashermes A., Mathieu E., Marinelli L., et al. Deciphering the mechanisms of action underlying probiotic properties of Shouchella clausii by a functional genomics approach. Benef Microbes. 2025; 16 (3): 347-362.

35. Li P., Han S., Wang M., et al. Elucidation of novel turnagainolides and their biosynthetic gene cluster in Bacillus subtilis. Appl Environ Microbiol. 2025; 91 (5): e0257424.

36. Paparo L., Tripodi L., Bruno C. Protective action of Bacillus clausii probiotic strains in an in vitro model of rotavirus infection. Sci. Rep. 2020; 10: 12636.

37. Lakshmi S. G., Jayanthi N., Saravanan M., Ratna M. S. Safety assesment of Bacillus clausii UBBC07, a spore forming probiotic. Toxicol Rep. 2017; 4: 62-71.

38. Urdaci M. C., Bressollier P., Pinchuk I. Bacillus clausii probiotic strains: Antimicrobial and immunomodulatory activities. J. Clin. Gastroenterol. 2004; 38: S86–S90.

39. Ripert G., Racedo S. M., Elie A. M., et al. Secreted compounds of the probiotic Bacillus clausii strain O/C Inhibit the cytotoxic effects induced by Clostridium difficile and Bacillus cereus toxins. Antimicrob. Agents Chemother. 2016; 60: 3445-3454.

40. Franciosa G., Guida S., Gomez Miguel M. J., et al. Live biotherapeutic products and their regulatory framework in Italy and Europe. Ann. Ist. Super. Sanita. 2023; 59: 56-67.

41. Gueimonde M., Sanchez B., de Los Reyes-Gavilan C. G., et al. Antibiotic resistance in probiotic bacteria. Front. Microbiol. 2013; 4: 202.

42. Girlich D., Leclercq R., Naas T., et al. Molecular and biochemical characterization of the chromosome-encoded class A beta-lactamase BCL-1 from Bacillus clausii. Antimicrob. Agents Chemother. 2007; 51: 4009-4014.

43. Garrett W. S., Gordon J. I., Glimcher L. H. Homeostasis and inflammation in the intestine. Cell. 2010; 140: 859-870.

44. Zoetendal E. G., Raes J., van den Bogert B., et al. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates. ISME J. 2012; 6: 1415-1426.

45. Kleerebezem M., Hols P., Bernard E., et al. The extracellular biology of the lactobacilli. FEMS Microbiol. Rev. 2010; 34: 199-230.

46. Park H., Jung A. Y., Chang C. S., et al. Bacillus clausii, a foreshore-derived probiotic, attenuates allergic airway inflammation through downregulation of hypoxia signaling. J. Rhinol. 2020; 27: 108-116.

47. Cruz C. S., Franca W. W. M., de Arujo H. D. A., et al. In vitro and in vivo evaluation of Bacillus clausii against Schistosoma mansoni. Acta Trop. 2022; 235: 106669.

48. Maity C., Gupta A. K. Therapeutic efficacy of probiotic Alkalihalobacillus clausii 088AE in antibiotic-associated diarrhea: A randomized controlled trial. Heliyon. 2021; 7: e07993.

49. Dang H. T., Tran D. M., Phung T. T. B., et al. Promising clinical and immunological efficacy of Bacillus clausii spore probiotics for supportive treatment of persistent diarrhea in children. Sci. Rep. 2024; 14: 6422.

50. Smiian K., Bynda T., Smiyan, et al. Bacillus clausii in treatment of rotavirus infection in children. Medicina. 2020; 56: 225.

51. Vazquez-Frias R., Consuelo-Sanchez A., Acosta-Rodriguez-Bueno C. P., et al. Efficacy and safety of the adjuvant use of probiotic Bacillus clausii strains in pediatric irritable bowel syndrome: A randomized, double-blind, placebo-controlled study. Pediatr. Drugs 2023; 25: 115-126.

52. Nirmala M., Smitha S. G., Kamath G. J. A study to assess the efficacy of local application of oral probiotic in treating recurrent aphthous ulcer and oral candidiasis. Indian J. Otolaryngol. Head Neck Surg. 2019; 71: 113-117.

53. Buhai M. C., Candrea R., Gavrilai L. I., еt al. Transforming Psoriasis Care: Probiotics and Prebiotics as Novel Therapeutic Approaches. Int J Mol Sci. 2023; 24 (13): 11225.

54. Wauters L ., Slaets H., Paepe K. D., et al. Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2021; 6 (10): 784-792.

55. Soman R. J., Swamy M. V. A prospective, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of SNZ TriBac, a three-strain Bacillus probiotic blend for undiagnosed gastrointestinal discomfort. Int. J. Color. Dis. 2019; 34: 1971-1978.

56. Tewari V. V., Dubey S. K., Gupta G. Bacillus clausii for prevention of late-onset sepsis in preterm infants: A randomized controlled trial. J. Trop. Pediatr. 2015; 61: 377-385.

57. Marseglia G. L., Tosca M., Cirillo I., et al. Efficacy of Bacillus clausii spores in the prevention of recurrent respiratory infections in children: A pilot study. Ther. Clin. Risk Manag. 2007; 3: 13-17.

58. Dhanasekhar K., Shyamala J., Arya K. Single-Strain Probiotics For The Management Of Acute Diarrhea In Children: A Randomized Comparative Study. Neuro Quantology. 2022; 20 (9): 5277-5283.