Potential use of synbiotics in ENT diseases

Prevention of recurrent ARVI is an urgent medical and social problem, especially in children. In children of this group, an imbalance of the intestinal flora was detected, which can be leveled by oral administration of probiotics, which cause immunomodulatory effects.

Normal micro-flora performs important physiological functions and are active against pathogenic and conditionally pathogenic microflora. The microbiota (a collection of microbes that colonize the human body) is affected by the environment, often leading to the development of SARS. In this case, the normal microflora has an antagonistic activity in relation to the pathogenic one. Useful bacteria are called probiotics (lactobacilli and bifidobacteria) and represent a treatment option for chronic respiratory diseases.

During the recurrence of acute respiratory infections (ROIDP), intestinal flora dysbiosis is detected, which can be improved by the use of probiotics.

Known diseases that disrupt the function of normal microflora, causing dysbiosis.

There are microorganisms that violate the permeability of the epithelial barrier of the mucous membrane. Dysbiosis can be regulated by probiotics that are administered both orally and nasally. They can have various immunomodulatory effects. Prebiotics are an indigestible form of fiber. A combination of Pro-and prebiotics is a synbiotic that has a synergistic effect in the treatment of many diseases and reduces the frequency of all infectious diseases.

New synbiotic dietary supplement contributes to the improvement of immunological mechanisms, mucosal immunity, enhancement of antiviral immunity, etc. It contains 5 probiotics and one prebiotic and is approved for use in children from the first month of life. This supplement has a positive effect on several immune system indicators in the treatment of sickly children. It may be recommended for dysbiosis, diabetes, coeliac disease and for the prevention of influenza and flu-like syndromes.

1. Zajac A.E., Adams A.S., Turner J.H. A systematic review and meta-analysis of probiotics for the treatment of allergic rhinitis. Int Forum Allergy Rhinol. 2015;5(6):524-532. doi: 10.1002/alr.21492.

2. Morris A., Beck J.M., Schloss P.D., Campbell T.B., Crothers K., Curtis J.L. et al. Lung HIV Microbiome Project. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med. 2013;187(10):1067-1075. doi: 10.1164/rccm.201210-1913OC.

3. Bassis C.M., Erb-Downward J.R., Dickson R.P. et al. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. mBio. 2015;6(2):e00037. doi: 10.1128/mBio.00037-15.

4. O'Dwyer D.N., Dickson R.P., Moore B.B. The lung microbiome, immunity, and the pathogenesis of chronic lung disease. J Immunol. 2016;196(12):4839-4847. doi: 10.4049/jimmunol.1600279.

5. Gallacher D.J., Kotecha S. Respiratory microbiome of new-born infants. Front Pediatr. 2016;4:10. doi: 10.3389/fped.2016.00010.

6. Winslow C-EA. A new method of enumerating bacteria in air. Science. 1908;28(705):28-31.doi: 10.1126/science.28.705.28.

7. Bojkova N.E., Garashchenko T.I., Rybalkin S.V. The state of the oropharynx microbiota as a reflection of the body's health. Uchastkovyj pediatr = Local pediatrician. 2016;(2):3. (In Russ.)

8. Gentile A., Bardach A., Ciapponi A., Garcia-Marti S., Aruj P. et al. Epidemiology of community-acquired pneumonia in children of Latin America and the Caribbean: a systematic review and meta-analysis. Int J Infect Dis. 2012;16(1):5-15. doi: 10.1016/j.ijid.2011.09.013.

9. Chen J., Xu Z., Ou X., Wang M., Yang X., Li Q. Mannose-binding lectin polymorphisms and recurrent respiratory tract infection in Chinese children. Eur J Pediatr. 2009;168(11):1305-1313. doi: 10.1007/s00431-009-0924-1.

10. Santos-Valente E., Reisli I., Artac H., Ott R., Sanal O., Boztug K. A novel mutation in the complement component 3 gene in a patient with selective IgA deficiency. J Clin Immunol. 2013;33(1):127-133. doi: 10.1007/s10875-012-9775-z.

11. Jacobsen C.N., Rosenfeldt Nielsen V., Hayford A.E., M0ller P.L. et al. Screening of probiotic activities of forty-seven strains of Lactobacillus spp. By in vitro techniques and evaluation of the colonization ability of five selected strains in humans. Appl Environ Microbiol. 1999 Nov;65(11):4949-4956. Available at: https://www.ncbi.nlm.nih.gov/pubmed/10543808.

12. Ahrne S., Hagslatt M.L. Effect of lactobacilli on paracellular permeability in the gut. Nutrients. 2011;3(1):104-117 doi: 10.3390/nu3010104.

13. Morais M.B., Jacob C.M. The role of probiotics and prebiotics in pediatric practice. J Pediatr (Rio J). 2006;82(5 suppl):S189-S197. doi: 10.2223/JPED.1559.

14. Clarke T.B. Early Innate Immunity to bacterial infection in the lung is regulated systemically by the commensal microbiota via nod-like receptor ligands. Infect Immun. 2014;82(11):4596-4606. doi: 10.1128/IAI.02212-14.

15. Schuijt T.J., Lankelma J.M., Scicluna B.P., de Sousa e Melo F., Roelofs J.J., de Boer J.D. The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia. Gut. 2016;65(4):575-583. doi: doi:10.1136/gutjnl-2015-309728.

16. Gauguet S., D'Ortona S., Ahnger-Pier K., Duan B., Surana N.K., et al. Intestinal microbiota of mice influences resistance to Staphylococcus aureus pneumonia. Infect Immun. 2015;83(10):4003-4014. doi: 10.1128/IAI.00037-15.

17. Ursell L.K., Clemente J.C., Rideout J.R., Gevers D., Caporaso J.G., Knight R. The interpersonal and intrapersonal diversity of human-associated microbiota in key body sites. J Allergy Clin Immunol. 2012;129(5):1204-1208. doi: 10.1016/j.jaci.2012.03.010.

18. Lebeer S., Vanderleyden J., De Keersmaecker S.C. Genes and molecules of lactobacilli supporting probiotic action. Microbiol Mol Biol Rev. 2008;72(4):728-764. doi: 10.1128/MMBR.00017-08.

19. Lebeer S., Vanderleyden J., De Keersmaecker S.C. Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nat Rev Microbiol. 2010;8(3):171-184. doi: 10.1038/nrmicro2297.

20. Mack D.R., Ahrne S., Hyde L., Wei S., Hollingsworth M.A. Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut. 2003;52(6):827-833. doi: 10.1136/gut.52.6.827.

21. Rao R.K., Samak G. Protection and Restitution of Gut Barrier by Probiotics: nutritional and clinical implications. Curr Nutr Food Sci. 2013;9(2):99-107. doi: 10.2174/1573401311309020004.

22. Wells J.M. Immunomodulatory mechanisms of lactobacilli. Microb Cell Fact. 2011;10(1):17. doi: 10.1186/1475-2859-10-S1-S17.

23. Petersen C., Round J.L. Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol. 2014;16(7):1024-1033. doi: 10.1111/cmi.12308.

24. Hoggard M., Biswas K., Zoing M., Wagner Mackenzie B., Taylor M.W., Douglas R.G. Evidence of microbiota dysbiosis in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2017;7(3):230-239. doi: 10.1002/alr.21871.

25. Aurora R., Chatterjee D., Hentzleman J., Prasad G., Sindwani R., Sanford T. Contrasting the microbiomes from healthy volunteers and patients with chronic rhinosinusitis. JAMA Otolaryngol Head Neck Surg. 2013;139(12):1328-1338. doi: 10.1001/jamaoto.2013.5465.

26. Malik Z., Roscioli E., Murphy J., Ou J., Bassiouni A., Wormald P.J., Vreugde S. Staphylococcus aureus impairs the airway epithelial barrier in vitro. Int Forum Allergy Rhinol. 2015;5(6):551-556. doi: 10.1002/alr.21517.

27. Clarke T.B., Francella N., Huegel A., Weiser J.N. Invasive bacterial pathogens exploit TLR-mediated downregulation of tight junction components to facilitate translocation across the epithelium. Cell Host Microbe. 2011;9(5):404-414. doi: 10.1016/j.chom.2011.04.012.

28. Fijan S. Microorganisms with claimed probiotic properties: an overview of recent literature. Int J Environ Res Public Health. 2014;11(5):4745-4767. doi: 10.3390/ijerph110504745.

29. Bogaert D., Keijser B., Huse S., Rossen J., Veenhoven R. et al. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PLoS One. 2011;6(2):e17035. doi: 10.1371/journal.pone.0017035.

30. Pettigrew M.M., Laufer A.S., Gent J.F., Kong Y., Fennie K.P., Metlay J.P. Upper respiratory tract microbial communities, acute otitis media pathogens, and antibiotic use in healthy and sick children. Appl Environ Microbiol. 2012;78(17):6262-6270. doi: 10.1128/AEM.01051-12.

31. Stearns J.C., Davidson C.J., McKeon S., Whelan F.J., Fontes M.E. et al. Culture and molecular-based profiles show shifts in bacterial communities of the upper respiratory tract that occur with age. ISME J. 2015;9(5):1246-1259. doi: 10.1038/ismej.2014.250.

32. Koch S., Nusrat A. The life and death of epithelia during inflammation: lessons learned from the gut. Ann Rev Pathol. 2012;7:35-60. doi: 10.1146/annurev-pathol-011811-120905.

33. Steelant B., Farre R., Wawrzyniak P., Belmans J., Dekimpe E., Vanheel H. et al. Impaired barrier function in patients with house dust mite-induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression. J Allergy Clin Immunol. 2016;137(4):1043-1053.e5. doi: 10.1016/j.jaci.2015.10.050.

34. Shen L., Weber C.R., Raleigh D.R., Yu D., Turner J.R. Tight junction pore and leak pathways: a dynamic duo. Annu Rev Physiol. 2011;73:283-309. doi: 10.1146/annurev-physiol-012110-142150.

35. Steelant B., Seys S.F., Boeckxstaens G., Akdis C.A., Ceuppens J.L., Hellings P.W. Restoring airway epithelial barrier dysfunction: a new therapeutic challenge in allergic airway disease. Rhinology. 2016;54(3):195-205. doi: 10.4193/Rhin15.376.

36. Orlando A., Linsalata M., Notarnicola M., Tutino V., Russo F. Lactobacillus GG restoration of the gliadin induced epithelial barrier disruption: the role of cellular polyamines. BMC Microbiol. 2014;14:19. doi: 10.1186/14712180-14-19.

37. Resta-Lenert S., Barrett K.E. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut. 2003;52(7):988-997. doi: 10.1136/gut.52.7.988.

38. Spacova I., Petrova M., Fremau A., Pollaris L., Vanoirbeek J., Ceuppens J.L., Seys S., Lebeer S. Intranasal administration of probiotic Lactobacillus rhamnosus GG prevents birch pollen induced allergic asthma in a murine model. Allergy. 2019;74(1):100-110. doi: 10.1111/all.13502.

39. Habermann W., Zimmermann K., Skarabis H., Kunze R., Rusch V. Reduction of acute recurrence in patients with chronic ecurrent hypertrophic sinusitis by treatment with a bacterial immunostimulant (Enterococcus faecalis Bacteriae of human origin. Arzneimittelforschung. 2002;52(8):622-627. doi: 10.1055/s-0051-1299941.

40. Chen Y.S., Jan R.L., Lin Y.L.., Chen H.H., Wang J.Y. Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis. Pediatr Pulmonol. 2010;45(11):1111-1120. doi: 10.1002/ppul.21296.

41. Gutkowski P., Madalinski K., Grek M., Dmenska H., Syczewska M., Michalkiewicz J. Effect of orally administered probiotic strain Lactobacillus and Bifidobacterium in children with atopic asthma. Cent Eur J Med. 2010;35(4):233-238. https//www.researchgate.net/publication/288594330_Effect_of_orally_administered_probiotic_strains_Lactobacillus_and_Bifidobacterium_in_children_with_atopic_asthma.

42. Rose M.A., Stieglitz F., Koksal A., Schubert R., Schulze J., Zielen S. Efficacy of probiotic Lactobacillus GG on allergic sensitization and asthma in infants at risk. Clin Exp Allergy. 2010;40(9):1398-1405. doi: 10.1111/j.1365-2222.2010.03560.x.

43. Kharitonova L.A., Kucherya T.V. Using Probiotics in Pediatric Practice: Clinical Study Results. Doctor.Ru. 2016;(6):38-41. (In Russ.) Available at: https://journaldoctor.ru/catalog/pediatriya/primenenie-probiotika-v-pediatricheskoy-praktike-rezultaty-klinicheskogo-issledovaniya/

44. Morris A., Beck J.M., Schloss P.D., Campbell T.B., Crothers K., Curtis J.L. et al. Lung HIV Microbiome Project. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med. 2013;187(10):1067-1675. doi: 10.1164/rccm.201210-1913OC.

45. Bassis C.M., Erb-Downward J.R., Dickson R.P., Freeman C.M., Schmidt T.M., Young V.B. et al. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. mBio. 2015;6(2):e00037. doi: 10.1128/mBio.00037-15.

46. Georas S.N., Rezaee F. Epithelial barrier function: at the front line of asthma immunology and allergic airway inflammation. J Allergy Clin Immunol. 2014;134(3):509-520. doi: 10.1016/j.jaci.2014.05.049.

47. Steelant B., Farre R., Wawrzyniak P., Belmans J., Dekimpe E., Van Heel H. et al. Impaired barrier function in patients with house dust mite-induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression. J Allergy Clin Immunol. 2016;137(4):1043-1053.e5. doi: 10.1016/j.jaci.2015.10.050.

48. Steelant B., Seys S.F., Van Gerven L., Van Woensel M., Farre R., Wawrzyniak P. et al. Histamine and T helper cytokine-driven epithelial barrier dysfunction in allergic rhinitis. J Allergy Clin Immunol. 2018;141(3):951-963.e8. doi: 10.1016/j.jaci.2017.08.039.

49. Zelaya H., Tsukida K., Chiba E., Marranzino G., Alvarez S., Kitazawa H., Aguero G., Villena J. Immunobiotic lactobacilli reduce viral-associated pulmonary damage through the modulation of inflammation-coagulation interactions. Int Immunopharmacol. 2014;19(1):161-173. doi: 10.1016/j.intimp.2013.12.020.

50. Medina M., Villena J., Salva S., Vintini E., Langella P., Alvarez S. Nasal administration of Lactococcus lactis improves local and systemic immune responses against Streptococcus pneumoniae. Microbiol Immunol. 2008;52(8):399-409. doi: 10.1111/j.1348-0421.2008.00050.x.

51. Shandilya U.K., Jadhav S., Panwar V., Kansal V.K. Probiotics: potent immunomodulatory tool against allergy. Probiotics Antimicrob Proteins. 2011;3(3-4):151-158. doi: 10.1007/s12602-011-9077-4.

52. Chan C.K.Y., Tao J., Chan O.S., Li H.B., Pang H. Preventing Respiratory Tract Infections by Synbiotic Interventions: A Systematic Review and MetaAnalysis of Randomized Controlled Trials. Adv Nutr. 2020. pii: nmaa003. doi: 10.1093/advances/nmaa003.

53. Chapman C.M.C., Gibson G.R., Rowland I. In vitro evaluation of single and multi-strain probiotics: inter-species inhibition between probiotic strains and inhibition of pathogens. Anaerobe. 2012;18(4):405-413. doi: 10.1016/j.anaerobe.2012.05.004.

54. Zakharova I.N., Sugyan N.G., Ardatskaya M.D., Lazareva S.I. Experience with a multi-strain probiotic in infants with functional gastrointestinal disorders. Meditsinskiy sovet = Medical Council. 2015;(14):48-53. (In Russ.) doi: 10.21518/2079-701X-2015-14-48-53.

55. Garaschenko T.I., Levitskiy M.V., Ezhova V.V., Chekunov N.V., Kostryukova E.S. Options for safe antibiotic treatment for acute otitis media in children. Meditsinskiy sovet = Medical Council. 2015;(14):36-44. (In Russ.) doi: 10.21518/2079-701X-2015-14-36-44

56. Vlieger A.M., Robroch A., van Buuren S., Kiers J., Rijkers G., Benninga M.A., te Biesebeke R. Tolerance and safety of Lactobacillus paracasei ssp. paraca-sei in combination with Bifidobacterium animalis ssp. lactis in a prebiotic-containing infant formula: a randomised controlled trial. Br J Nutr. 2009;102(6):869-875. doi: 10.1017/S0007114509289069.

57. Gerasimov S.V., Ivantsiv V.A., Bobryk L.M., Tsitsura O.O., Dedyshin L.P., Guta N.V., Yandyo B.V. Role of short-term use of L. acidophilus DDS-1 and B. lactis UABLA-12 in acute respiratory infections in children: a randomized controlled trial. Eur J Clin Nutr 2016;70(4):463-469. doi: 10.1038/ejcn.2015.171.

58. Cohen R., Martin E., de La Rocque F., Thollot F., Pecquet S., Werner A., et al. Probiotics and prebiotics in preventing episodes of acute otitis media in high-risk children: a randomized, double-blind, placebo-controlled study. Pediatr Infect Dis J. 2013;32(8):810-814. doi: 10.1097/INF.0b013e31828df4f3.

59. Sazawal S., Dhingra U., Hiremath G., Sarkar A., Dhingra P. et al. Prebiotic and probiotic fortified milk in prevention of morbidities among children: communitybased, randomized, double-blind, controlled trial. PLoS One. 2010;5(8):e12164. doi: 10.1371/journal.pone.0012164.

60. Puccio G., Cajozzo C., Meli F., Rochat F., Grathwohl D., Steenhout P. Clinical evaluation of a new starter formula for infants containing live Bifidobacterium longum BL999 and prebiotics. Nutrition. 2007;23(1):1-8. doi: 10.1016/j.nut.2006.09.007.

61. Xuan N.N., Wang D., Grathwohl D., Lan P.N.T., Kim H.V.T., Goyer A., Benyacoub J. Effect of a growing-up milk containing synbiotics on immune function and growth in children: a cluster randomized, multicenter, double-blind, placebo controlled study. Clin Med Insights Pediatr. 2013;7:49-56. doi: 10.4137/CMPed.S13073.

62. Bocquet A., Lachambre E., Kempf C., Beck L. Effect of infant and follow-on formulas containing B lactis and galacto- and fructooligosaccharides on infection in healthy term infants. J Pediatr Gastroenterol Nutr. 2013;57(2):180-187. doi: 10.1097/MPG.0b013e318297f35e.

63. Hill C., Guarner F., Reid G., Gibson G.R., Merenstein D.J., Pot B. et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514. doi: 10.1038/nrgastro.2014.66.

64. Ketlinskiy S.A. The IL-17 family cytokines and it biological function. Medit sin skiy akademicheskiy zhurnal = Medical academic journal. 2006;6(2):12-27. (In Russ.)

65. Kologrivova I.V., Kologrivova Y.N., Suslova T.Y. Molecular aspects of the T-helpers type 17 functioning. Byulleten' sibirskoy meditsiny = Bulletin of Siberian Medicine. 2011;10(4):93-98. (In Russ.) doi: 10.20538/1682-0363-2011-4-93-98.

66. Kornilina E.M., Nikolayenko A.N., Volk A.D. et al. A new drug in the treatment of chronic hepatitis C. Visnikfarmakologii ta farmatsii = Herald of pharmacology and pharmacy. 2005;(5):24-27. (In Russ.) Available at: http://www.book.lib-i.ru/25meditsina/521011-1-noviy-preparat-lechenii-hronicheskogo-gepatita-emkornilina-annikolaenko-npc-erbis.php.

67. Chopyak V.V., Potemkina G.A., Bilyanskaya L.N., Kril' I.I., Mzurak M.V., Lishchuk-Yakimovich K.A. Immune regulatory mechanisms studies and their possible correction in frequently ill children. Sovremennaya pediatriya = Modern Pediatrics. 2015;(3):85-91. (In Russ.) doi: 10.15574/SP.2015.67.85.

68. Sheih Y.H., Chiang B.L., Wang L.H. Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001. J Am Coll Nutr. 2001;20(2 Suppl):149-156. doi: 10.1080/07315724.2001.10719027.