medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2022-127medsovet-7357Research ArticleБРОНХОПУЛЬМОНОЛОГИЯ И ОТОЛАРИНГОЛОГИЯBRONCHOPULMONOLOGY, OTORHINOLARYNGOLOGYИзменчивые и коварные респираторные инфекции: можно ли их предупредить?Variable and insidious respiratory infections: can they be prevented?https://orcid.org/0000-0003-3426-3426ЗайцеваО. В.ZaytsevaO. V.

Зайцева Ольга Витальевна - доктор медицинских наук, профессор, заведующая кафедрой педиатрии, МГМСУ им. А.И. Евдокимова; врач приемного отделения – врач-педиатр, ДГКБ святого Владимира.

127473, Москва, ул. Делегатская, д. 20, стр. 1; 107014, Москва, ул. Рубцовско-Дворцовая, д. 1/3, корп. 1

Olga V. Zaytseva - Dr. Sci. (Med.), Professor, Head of the Department of Pediatrics, Yevdokimov Moscow State University of Medicine and Dentistry; Doctor of the Admission Department – Pediatrician, Children’s City Clinical Hospital of St. Vladimir.

20, Bldg. 1, Delegateskaya St., Moscow, 127473; 1/3, Bldg. 1, Rubtsovsko-Dvortsovaya St., Moscow, 107014

olga6505963@yandex.ruРычковаТ. И.RychkovaT. I.

Рычкова Татьяна Ивановна - кандидат медицинских наук, доцент кафедры педиатрии.

127473, Москва, ул. Делегатская, д. 20, стр. 1

Tatiana I. Rychkova - Cand. Sci. (Med.), Associate Professor of the Department of Pediatrics, Yevdokimov Moscow State University of Medicine and Dentistry.

20, Bldg. 1, Delegatskaya St., Moscow, 127473

tatrychkova@gmail.comhttps://orcid.org/0000-0001-6006-7846ЛокшинаЭ. Э.LokshinaE. E.

Локшина Эвелина Эдуардовна - кандидат медицинских наук, профессор кафедры педиатрии.

127473, Москва, ул. Делегатская, д. 20, стр. 1

Evelina E. Lokshina - Cand. Sci. (Med.), Professor of the Department of Pediatrics, Yevdokimov Moscow State University of Medicine and Dentistry.

20, Bldg. 1, Delegateskaya St., Moscow, 127473

elokshina@yandex.ruhttps://orcid.org/0000-0001-5115-6185ШумейкоН. К.ShumeikoN. K.

Шумейко Наталья Константиновна - кандидат медицинских наук, доцент кафедры педиатрии, заведующий учебной частью факультета дополнительного профессионального образования.

127473, Москва, ул. Делегатская, д. 20, стр. 1

Natalia K. Shumeiko - Cand. Sci. (Med.), Associate Professor of the Department of Pediatrics, Head of the Academic Department of the Faculty of Additional Professional Education, Yevdokimov Moscow State University of Medicine and Dentistry.

20, Bldg. 1, Delegateskaya St., Moscow, 127473

shumnatalia@yandex.ruhttps://orcid.org/0000-0002-5141-0304КуликоваЕ. В.KulikovaE. V.

Куликова Елена Вильевна - кандидат медицинских наук, доцент кафедры педиатрии, заведующий учебной частью.

127473, Москва, ул. Делегатская, д. 20, стр. 1

Elena V. Kulikova - Cand. Sci. (Med.), Associate Professor of the Department of Pediatrics, Head of the Academic Department, Yevdokimov Moscow State University of Medicine and Dentistry.

20, Bldg. 1, Delegateskaya St., Moscow, 127473

ev_kulikova@mail.ruМосковский государственный медико-стоматологический университет имени А.И. Евдокимова; Детская городская клиническая больница святого ВладимираРоссияYevdokimov Moscow State University of Medicine and Dentistry; Children’s City Clinical Hospital of St. VladimirRussian FederationМосковский государственный медико-стоматологический университет имени А.И. ЕвдокимоваРоссияYevdokimov Moscow State University of Medicine and DentistryRussian Federation202312032023013945Copyright © Зайцева О.В., Рычкова Т.И., Локшина Э.Э., Шумейко Н.К., Куликова Е.В., 20232023Зайцева О.В., Рычкова Т.И., Локшина Э.Э., Шумейко Н.К., Куликова Е.В.Zaytseva O.V., Rychkova T.I., Lokshina E.E., Shumeiko N.K., Kulikova E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7357

В практике педиатра среди всех выявляемых инфекционных заболеваний продолжают лидировать острые респираторные заболевания. Причины возникновения респираторных инфекций могут быть разнообразными. Важное значение имеет нормальная микрофлора как один из главных регуляторных факторов, способных обеспечить адаптацию детей к разным условиям жизни, которая является ответственной за поддержание гомеостаза и созревания иммунной системы. В настоящее время установлено, что здоровый микробиом ротовой полости является залогом соматического здоровья и одним из важных составляющих противоинфекционной защиты. Поэтому актуально и перспективно направление профилактики респираторных инфекций посредством применения пероральных пробиотиков. В статье приведен обзор результатов исследований эффективности и безопасности пробиотического штамма Streptococcus salivarius K12, обладающего ингибирующей активностью в отношении основных респираторных патогенов – Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis. S. salivarius K12 продуцирует бактериоциноподобную ингибиторную субстанцию BLIS K12 (Вacteriocin-Like Inhibitory Substance), которая играет важную роль в сохранении естественной микрофлоры верхних дыхательных путей. Доказано, что применение S. salivarius K12 приводит к снижению степени колонизации слизистой оболочки ротоглотки патогенами, быстрому уменьшению клинических симптомов острых и хронических заболеваний лор-органов, профилактике острых респираторных заболеваний. Это объясняется тем, что прием S. salivarius K12 увеличивает количество интерферона γ в слюне, стимулируя адаптивный иммунитет против многих вирусных инфекций. S. salivarius K12 внесен в клинические рекомендации «Острый тонзиллофарингит» для профилактики рецидивов, а также восстановления нормобиоты слизистой оболочки ротоглотки после перенесенного заболевания.

In the practice of a pediatrician, among all detected infectious diseases, acute respiratory infections (ARI) continue to lead. The causes of respiratory infections can be varied. Great importance is attached to the normal microflora, as one of the main regulatory factors that can ensure the adaptation of children to different living conditions, and is responsible for maintaining homeostasis and maturation of the immune system. It has now been established that a healthy oral microbiome is the key to somatic health, and one of the important components of anti-infective protection. Therefore, one of the promising areas for the prevention of respiratory infections is the use of oral probiotics. The article provides an overview of findings from the studies on the efficacy and safety of the probiotic strain Streptococcus salivarius K12 showing inhibitory activities against the main respiratory pathogens – Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis. S. salivarius K12 produces the bacteriocin-like inhibitory substance BLIS K12 (Bacteriocin-Like Inhibitory Substance), which plays an important role in maintaining the natural flora of the upper respiratory tract. It has been proven that the use of S. salivarius K12 results in a reduction of the level of pathogen colonization of the oropharyngeal mucosa, a rapid decline of the clinical symptoms of acute and chronic diseases of the ENT organs, and the prevention of acute respiratory diseases. The reason for this is that the intake of S. salivarius K12 increases the amount of interferon γ in saliva, stimulating the adaptive immunity against many viral infections. S. salivarius K12 is included in the clinical guideline on acute tonsillopharyngitis for the prevention of relapses, as well as the recovery of the normal biota of the oropharyngeal mucosa after disease.

острое респираторное заболеваниедетимикробиом полости ртапрофилактикапробиотикиStreptococcus salivarius K12acute respiratory infectionschildrenoral microbiomepreventionprobioticsStreptococcus salivarius K12ReferencesWalsh T., Macey R., Riley P., Glenny A.M., Schwendicke F., Worthington H.V. et al. Imaging modalities to inform the detection and diagnosis of early caries. Cochrane Database Syst Rev. 2021;3(3):CD014545. https://doi.org/10.1002/14651858.cd014545.Walsh T., Macey R., Riley P., Glenny A.M., Schwendicke F., Worthington H.V. et al. Imaging modalities to inform the detection and diagnosis of early caries. Cochrane Database Syst Rev. 2021;3(3):CD014545. https://doi.org/10.1002/14651858.cd014545.Pujia A.M., Costacurta M., Fortunato L., Merra G., Cascapera S., Calvani M., Gratteri S. The probiotics in dentistry: a narrative review. Eur Rev Med Pharmacol Sci. 2017;21(6):1405–1412. Available at: https://www.european-review.org/article/12422.Pujia A.M., Costacurta M., Fortunato L., Merra G., Cascapera S., Calvani M., Gratteri S. The probiotics in dentistry: a narrative review. Eur Rev Med Pharmacol Sci. 2017;21(6):1405–1412. Available at: https://www.european-review.org/article/12422.Aagaard K., Ma J., Antony K.M., Ganu R., Petrosino J., Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6(237):237ra65. https://doi.org/10.1126/scitranslmed.3008599.Aagaard K., Ma J., Antony K.M., Ganu R., Petrosino J., Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6(237):237ra65. https://doi.org/10.1126/scitranslmed.3008599.Bearfield C., Davenport E.S., Sivapathasundaram V., Allaker R.P. Possible association between amniotic fluid micro-organism infection and microflora in the mouth. BJOG. 2002;109(5):527–533. https://doi.org/10.1111/j.1471-0528.2002.01349.x.Bearfield C., Davenport E.S., Sivapathasundaram V., Allaker R.P. Possible association between amniotic fluid micro-organism infection and microflora in the mouth. BJOG. 2002;109(5):527–533. https://doi.org/10.1111/j.1471-0528.2002.01349.x.Jiménez E., Marín M.L., Martín R., Odriozola J.M., Olivares M., Xaus J. et al. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008;159(3):187–193. https://doi.org/10.1016/j.resmic.2007.12.007.Jiménez E., Marín M.L., Martín R., Odriozola J.M., Olivares M., Xaus J. et al. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008;159(3):187–193. https://doi.org/10.1016/j.resmic.2007.12.007.Rautava S., Collado M.C., Salminen S., Isolauri E. Probiotics modulate host-microbe interaction in the placenta and fetal gut: a randomized, double-blind, placebo-controlled trial. Neonatology. 2012;102(3):178–184. https://doi.org/10.1159/000339182.Rautava S., Collado M.C., Salminen S., Isolauri E. Probiotics modulate host-microbe interaction in the placenta and fetal gut: a randomized, double-blind, placebo-controlled trial. Neonatology. 2012;102(3):178–184. https://doi.org/10.1159/000339182.Steel J.H., Malatos S., Kennea N., Edwards A.D., Miles L., Duggan P. et al. Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor. Pediatr Res. 2005;57(3):404–411. https://doi.org/10.1203/01.PDR.0000153869.96337.90.Steel J.H., Malatos S., Kennea N., Edwards A.D., Miles L., Duggan P. et al. Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor. Pediatr Res. 2005;57(3):404–411. https://doi.org/10.1203/01.PDR.0000153869.96337.90.Stout M.J., Conlon B., Landeau M., Lee I., Bower C., Zhao Q. et al. Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations. Am J Obstet Gynecol. 2013;208(3):226.e1–7. https://doi.org/10.1016/j.ajog.2013.01.018.Stout M.J., Conlon B., Landeau M., Lee I., Bower C., Zhao Q. et al. Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations. Am J Obstet Gynecol. 2013;208(3):226.e1–7. https://doi.org/10.1016/j.ajog.2013.01.018.Walton G.E., Gibson G.R., Hunter K.A. Mechanisms linking the human gut microbiome to prophylactic and treatment strategies for COVID-19. Br J Nutr. 2021;126(2):219–227. https://doi.org/10.1017/S0007114520003980.Walton G.E., Gibson G.R., Hunter K.A. Mechanisms linking the human gut microbiome to prophylactic and treatment strategies for COVID-19. Br J Nutr. 2021;126(2):219–227. https://doi.org/10.1017/S0007114520003980.Wang Y., Li X., Ge T., Xiao Y., Liao Y., Cui Y. et al. Probiotics for prevention and treatment of respiratory tract infections in children: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2016;95(31):e4509. https://doi.org/10.1097/MD.0000000000004509.Wang Y., Li X., Ge T., Xiao Y., Liao Y., Cui Y. et al. Probiotics for prevention and treatment of respiratory tract infections in children: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2016;95(31):e4509. https://doi.org/10.1097/MD.0000000000004509.Man W.H., van Houten M.A., Mérelle M.E., Vlieger A.M., Chu M.L.J.N., Jansen N.J.G. et al. Bacterial and viral respiratory tract microbiota and host characteristics in children with lower respiratory tract infections: a matched case-control study. Lancet Respir Med. 2019;7(5):417–426. https://doi.org/10.1016/S2213-2600(18)30449-1.Man W.H., van Houten M.A., Mérelle M.E., Vlieger A.M., Chu M.L.J.N., Jansen N.J.G. et al. Bacterial and viral respiratory tract microbiota and host characteristics in children with lower respiratory tract infections: a matched case-control study. Lancet Respir Med. 2019;7(5):417–426. https://doi.org/10.1016/S2213-2600(18)30449-1.Prescott S.L., Larcombe D.L., Logan A.C., West C., Burks W., Caraballo L. et al. The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming. World Allergy Organ J. 2017;10(1):29. https://doi.org/10.1186/s40413-017-0160-5.Prescott S.L., Larcombe D.L., Logan A.C., West C., Burks W., Caraballo L. et al. The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming. World Allergy Organ J. 2017;10(1):29. https://doi.org/10.1186/s40413-017-0160-5.Овчинников А.Ю., Мирошниченко Н.А., Егиян С.С., Акопян Л.В. Возможности пробиотической терапии при хронических воспалительных заболеваниях ротоглотки. Эффективная фармакотерапия. 2022;18(4):24–28. Режим доступа: https://umedp.ru/articles/vozmozhnosti_probioticheskoy_terapii_pri_khronicheskikh_vospalitelnykh_zabolevaniyakh_rotoglotki.html.Ovchinnikov A.Yu., Miroshnichenko N.A., Egiyan S.S., Akopyan L.V. Possibilities of probiotic therapy in chronic inflammatory diseases of the oropharynx. Effective Pharmacotherapy. 2022;18(4):24–28. (In Russ.) Available at: https://umedp.ru/articles/vozmozhnosti_probioticheskoy_terapii_pri_khronicheskikh_vospalitelnykh_zabolevaniyakh_rotoglotki.html.Burton J.P., Cowley S., Simon R.R., McKinney J., Wescombe P.A., Tagg J.R. Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study. Food Chem Toxicol. 2011;49(9):2356–2364. https://doi.org/10.1016/j.fct.2011.06.038.Burton J.P., Cowley S., Simon R.R., McKinney J., Wescombe P.A., Tagg J.R. Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study. Food Chem Toxicol. 2011;49(9):2356–2364. https://doi.org/10.1016/j.fct.2011.06.038.Wescombe P.A., Hale J.D., Heng N.C., Tagg J.R. Developing oral probiotics from Streptococcus salivarius. Future Microbiol. 2012;7(12):1355–1371. https://doi.org/10.2217/fmb.12.113.Wescombe P.A., Hale J.D., Heng N.C., Tagg J.R. Developing oral probiotics from Streptococcus salivarius. Future Microbiol. 2012;7(12):1355–1371. https://doi.org/10.2217/fmb.12.113.Hod K., Ringel Y. Probiotics in functional bowel disorders. Best Pract Res Clin Gastroenterol. 2016;30(1):89–97. https://doi.org/10.1016/j.bpg.2016.01.003.Hod K., Ringel Y. Probiotics in functional bowel disorders. Best Pract Res Clin Gastroenterol. 2016;30(1):89–97. https://doi.org/10.1016/j.bpg.2016.01.003.Di Pierro F., Colombo M., Giuliani M.G., Danza M.L., Basile I., Bollani T. et al. Effect of administration of Streptococcus salivarius K12 on the occurrence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3 years old children. Eur Rev Med Pharmacol Sci. 2016;20(21):4601–4606. Available at: https://www.europeanreview.org/article/11696.Di Pierro F., Colombo M., Giuliani M.G., Danza M.L., Basile I., Bollani T. et al. Effect of administration of Streptococcus salivarius K12 on the occurrence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3 years old children. Eur Rev Med Pharmacol Sci. 2016;20(21):4601–4606. Available at: https://www.europeanreview.org/article/11696.Di Pierro F., Colombo M., Zanvit A., Risso P., Rottoli A.S. Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children. Drug Healthc Patient Saf. 2014;6:15–20. https://doi.org/10.2147/DHPS.S59665.Di Pierro F., Colombo M., Zanvit A., Risso P., Rottoli A.S. Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children. Drug Healthc Patient Saf. 2014;6:15–20. https://doi.org/10.2147/DHPS.S59665.Di Pierro F., Campana A., Panatta M.L., et al. The use of Streptococcus salivarius K12 in attenuating PFAPA syndrome, a pilot study. Altern Integr Med. 2016;5(4):222. https://doi.org/10.4172/2327-5162.1000222.Di Pierro F., Campana A., Panatta M.L., et al. The use of Streptococcus salivarius K12 in attenuating PFAPA syndrome, a pilot study. Altern Integr Med. 2016;5(4):222. https://doi.org/10.4172/2327-5162.1000222.Sahl H.G., Bierbaum G. Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria. Annu Rev Microbiol. 1998;52:41–79. https://doi.org/10.1146/annurev.micro.52.1.41.Sahl H.G., Bierbaum G. Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria. Annu Rev Microbiol. 1998;52:41–79. https://doi.org/10.1146/annurev.micro.52.1.41.Крючко Т.О., Ткаченко О.Я. Можливості застосування лантибіотиків у профілактиці рекурентних інфекцій верхніх дихальних шляхів у дітей. Здоровье ребенка. 2017;12(8):13–18. Режим доступа: http://pediatric.mifua.com/archive/article/45461.Kryuchko T.O., Tkachenko O.Ya. Possibilities of using lantibiotics to prevent recurrent upper respiratory tract infections in children. Child’s Health. 2017;12(8):13–18. (In Ukrainian). Available at: http://pediatric.mif-ua.com/archive/article/45461.Tagg J.R. Prevention of streptococcal pharyngitis by anti-Streptococcus pyogenes bacteriocin-like inhibitory substances (BLIS) produced by Streptococcus salivarius. Indian J Med Res. 2004;119(Suppl.):13–16. Available at: https://pubmed.ncbi.nlm.nih.gov/15232154/.Tagg J.R. Prevention of streptococcal pharyngitis by anti-Streptococcus pyogenes bacteriocin-like inhibitory substances (BLIS) produced by Streptococcus salivarius. Indian J Med Res. 2004;119(Suppl.):13–16. Available at: https://pubmed.ncbi.nlm.nih.gov/15232154/.Hyink O., Wescombe P.A., Upton M., Ragland N., Burton J.P., Tagg J.R. Salivaricin A2 and the novel lantibiotic salivaricin B are encoded at adjacent loci on a 190-kilobase transmissible megaplasmid in the oral probiotic strain Streptococcus salivarius K12. Appl Environ Microbiol. 2007;73(4):1107–1113. https://doi.org/10.1128/AEM.02265-06.Hyink O., Wescombe P.A., Upton M., Ragland N., Burton J.P., Tagg J.R. Salivaricin A2 and the novel lantibiotic salivaricin B are encoded at adjacent loci on a 190-kilobase transmissible megaplasmid in the oral probiotic strain Streptococcus salivarius K12. Appl Environ Microbiol. 2007;73(4):1107–1113. https://doi.org/10.1128/AEM.02265-06.Sharma S., Verma K.K. Skin and soft tissue infection. Indian J Pediatr. 2001;68(Suppl. 3):S46–50. Available at: https://pubmed.ncbi.nlm.nih.gov/11980459/.Sharma S., Verma K.K. Skin and soft tissue infection. Indian J Pediatr. 2001;68(Suppl. 3):S46–50. Available at: https://pubmed.ncbi.nlm.nih.gov/11980459/.Wescombe P.A., Burton J.P., Cadieux P.A., Klesse N.A., Hyink O., Heng N.C. et al. Megaplasmids encode differing combinations of lantibiotics in Streptococcus salivarius. Antonie Van Leeuwenhoek. 2006;90(3):269–280. https://doi.org/10.1007/s10482-006-9081-y.Wescombe P.A., Burton J.P., Cadieux P.A., Klesse N.A., Hyink O., Heng N.C. et al. Megaplasmids encode differing combinations of lantibiotics in Streptococcus salivarius. Antonie Van Leeuwenhoek. 2006;90(3):269–280. https://doi.org/10.1007/s10482-006-9081-y.Stowik T.A. Contribution of Probiotics Streptococcus salivarius Strains K12 and M18 to Oral Health in Humans: A Review. Honors Scholar Theses. 2016:488. Available at: https://opencommons.uconn.edu/srhonors_theses/488.Stowik T.A. Contribution of Probiotics Streptococcus salivarius Strains K12 and M18 to Oral Health in Humans: A Review. Honors Scholar Theses. 2016:488. Available at: https://opencommons.uconn.edu/srhonors_theses/488.Пальчун В.Т., Крюков А.И., Магомедов М.М. (ред.). Руководство по очаговой инфекции в оториноларингологии. М.: ГЭОТАР-Медиа; 2015. 224 с.Palchun V.T., Kryukov A.I., Magomedov M.M. (eds.). Guide to focal infection in otorhinolaryngology. Moscow: GEOTAR-Media; 2015. 224 p. (In Russ.)Abt M.C., Osborne L.C., Monticelli L.A., Doering T.A., Alenghat T., Sonnenberg G.F. et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity. 2012;37(1):158–170. https://doi.org/10.1016/j.immuni.2012.04.011.Abt M.C., Osborne L.C., Monticelli L.A., Doering T.A., Alenghat T., Sonnenberg G.F. et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity. 2012;37(1):158–170. https://doi.org/10.1016/j.immuni.2012.04.011.Wescombe P.A., Heng N.C., Burton J.P., Tagg J.R. Something Old and Something New: An Update on the Amazing Repertoire of Bacteriocins Produced by Streptococcus salivarius. Probiotics Antimicrob Proteins. 2010;2(1):37–45. https://doi.org/10.1007/s12602-009-9026-7.Wescombe P.A., Heng N.C., Burton J.P., Tagg J.R. Something Old and Something New: An Update on the Amazing Repertoire of Bacteriocins Produced by Streptococcus salivarius. Probiotics Antimicrob Proteins. 2010;2(1):37–45. https://doi.org/10.1007/s12602-009-9026-7.Venekamp R.P., Burton M.J., van Dongen T.M., van der Heijden G.J., van Zon A., Schilder A.G. Antibiotics for otitis media with effusion in children. Cochrane Database Syst Rev. 2016;(6):CD009163. https://doi.org/10.1002/14651858.CD009163.pub3.Venekamp R.P., Burton M.J., van Dongen T.M., van der Heijden G.J., van Zon A., Schilder A.G. Antibiotics for otitis media with effusion in children. Cochrane Database Syst Rev. 2016;(6):CD009163. https://doi.org/10.1002/14651858.CD009163.pub3.Horz H.P., Meinelt A., Houben B., Conrads G. Distribution and persistence of probiotic Streptococcus salivarius K12 in the human oral cavity as determined by real-time quantitative polymerase chain reaction. Oral Microbiol Immunol. 2007;22(2):126–130. https://doi.org/10.1111/j.1399-302X.2007.00334.x.Horz H.P., Meinelt A., Houben B., Conrads G. Distribution and persistence of probiotic Streptococcus salivarius K12 in the human oral cavity as determined by real-time quantitative polymerase chain reaction. Oral Microbiol Immunol. 2007;22(2):126–130. https://doi.org/10.1111/j.1399-302X.2007.00334.x.Power D.A., Burton J.P., Chilcott C.N., Dawes P.J., Tagg J.R. Preliminary investigations of the colonisation of upper respiratory tract tissues of infants using a paediatric formulation of the oral probiotic Streptococcus salivarius K12. Eur J Clin Microbiol Infect Dis. 2008;27(12):1261–123. https://doi.org/10.1007/s10096-008-0569-4.Power D.A., Burton J.P., Chilcott C.N., Dawes P.J., Tagg J.R. Preliminary investigations of the colonisation of upper respiratory tract tissues of infants using a paediatric formulation of the oral probiotic Streptococcus salivarius K12. Eur J Clin Microbiol Infect Dis. 2008;27(12):1261–123. https://doi.org/10.1007/s10096-008-0569-4.Савлевич Е.Л., Дорощенко Н.Э., Жарких М.А., Маркус П.В., Герасимов А.Н. Коррекция галитоза при хронических воспалительных заболеваниях ротоглотки у взрослых. Вестник оториноларингологии. 2021;86(6):41–46. https://doi.org/10.17116/otorino20218606141.Savlevich E.L., Doroshchenko N.E., Zharkikh M.A., Markus P.V., Gerasimov A.N. Correction of halitosis in chronic inflammatory diseases of the oropharynx in adults. Vestnik Oto-Rino-Laringologii. 2021;86(6):41–46. (In Russ.) https://doi.org/10.17116/otorino20218606141.Гострый А.В., Симонова А.В., Михайлова Н.А., Снимщикова И.А., Осипов Г.А., Агафонов Б.В. и др. Хронический фарингит: этиология, патогенез, лечение. Новые подходы к оценке этиопатогенеза. Архивъ внутренней медицины. 2019;9(1):32–43. https://doi.org/10.20514/2226-6704-2019-9-1-32-43.Gostry A.V., Simonova A.V., Mikhailova N.A., Snimshchikova I.A., Osipov G.A., Agafonov B.V. et al. Chronic pharyngitis: etiology, pathogenesis, treatment. New approaches to the estimation of etiopatogenesis. Russian Archives of Internal Medicine. 2019;9(1):32–43. (In Russ.) https://doi.org/10.20514/2226-6704-2019-9-1-32-43.Kinberg S., Stein M., Zion N., Shaoul R. The gastrointestinal aspects of halitosis. Can J Gastroenterol. 2010;24(9):552–556. https://doi.org/10.1155/2010/639704.Kinberg S., Stein M., Zion N., Shaoul R. The gastrointestinal aspects of halitosis. Can J Gastroenterol. 2010;24(9):552–556. https://doi.org/10.1155/2010/639704.Kapoor U., Sharma G., Juneja M., Nagpal A. Halitosis: Current concepts on etiology, diagnosis and management. Eur J Dent. 2016;10(2):292–300. https://doi.org/10.4103/1305-7456.178294.Kapoor U., Sharma G., Juneja M., Nagpal A. Halitosis: Current concepts on etiology, diagnosis and management. Eur J Dent. 2016;10(2):292–300. https://doi.org/10.4103/1305-7456.178294.Савлевич Е.Л., Симбирцев А.С., Чистякова Г.Н., Терехина К.Г., Бацкалевич Н.А. Состояние системного и местного иммунитета при острых назофарингитах на фоне ОРВИ. Терапия. 2021;7(4):57–63. https://doi.org/10.18565/therapy.2021.4.57-63.Savlevich E.L., Simbirtsev A.S., Chistyakova G.N., Terekhina K.G., Batskalevich N.A. The state of systemic and local immunity in acute nasopharyngitis against the background of SARS. Therapy. 2021;7(4):57–63. (In Russ.) https://doi.org/10.18565/therapy.2021.4.57-63.Burton J.P., Cowley S., Simon R.R., McKinney J., Wescombe P.A., Tagg J.R. Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study. Food Chem Toxicol. 2011;49(9):2356–2364. https://doi.org/10.1016/j.fct.2011.06.038.Burton J.P., Cowley S., Simon R.R., McKinney J., Wescombe P.A., Tagg J.R. Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study. Food Chem Toxicol. 2011;49(9):2356–2364. https://doi.org/10.1016/j.fct.2011.06.038.Burton J.P., Wescombe P.A., Moore C.J., Chilcott C.N., Tagg J.R. Safety assessment of the oral cavity probiotic Streptococcus salivarius K12. Appl Environ Microbiol. 2006;72(4):3050–3053. https://doi.org/10.1128/AEM.72.4.3050-3053.2006.Burton J.P., Wescombe P.A., Moore C.J., Chilcott C.N., Tagg J.R. Safety assessment of the oral cavity probiotic Streptococcus salivarius K12. Appl Environ Microbiol. 2006;72(4):3050–3053. https://doi.org/10.1128/AEM.72.4.3050-3053.2006.Gregori G., Righi O., Risso P., Boiardi G., Demuru G., Ferzetti A. et al. Reduction of group A beta-hemolytic streptococcus pharyngo-tonsillar infections associated with use of the oral probiotic Streptococcus salivarius K12: a retrospective observational study. Ther Clin Risk Manag. 2016;12:87–92. https://doi.org/10.2147/TCRM.S96134.Gregori G., Righi O., Risso P., Boiardi G., Demuru G., Ferzetti A. et al. Reduction of group A beta-hemolytic streptococcus pharyngo-tonsillar infections associated with use of the oral probiotic Streptococcus salivarius K12: a retrospective observational study. Ther Clin Risk Manag. 2016;12:87–92. https://doi.org/10.2147/TCRM.S96134.Di Pierro F., Di Pasquale D., Di Cicco M. Oral use of Streptococcus salivarius K12 in children with secretory otitis media: preliminary results of a pilot, uncontrolled study. Int J Gen Med. 2015;8:303–308. https://doi.org/10.2147/IJGM.S92488.Di Pierro F., Di Pasquale D., Di Cicco M. Oral use of Streptococcus salivarius K12 in children with secretory otitis media: preliminary results of a pilot, uncontrolled study. Int J Gen Med. 2015;8:303–308. https://doi.org/10.2147/IJGM.S92488.Di Pierro F., Adami T., Rapacioli G., Giardini N., Streitberger C. Clinical evaluation of the oral probiotic Streptococcus salivarius K12 in the prevention of recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes in adults. Expert Opin Biol Ther. 2013;13(3):339–343. https://doi.org/10.1517/14712598.2013.758711.Di Pierro F., Adami T., Rapacioli G., Giardini N., Streitberger C. Clinical evaluation of the oral probiotic Streptococcus salivarius K12 in the prevention of recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes in adults. Expert Opin Biol Ther. 2013;13(3):339–343. https://doi.org/10.1517/14712598.2013.758711.Di Pierro F., Donato G., Fomia F., Adami T., Careddu D., Cassandro C., Albera R. Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media. Int J Gen Med. 2012;5:991–997. https://doi.org/10.2147/IJGM.S38859.Di Pierro F., Donato G., Fomia F., Adami T., Careddu D., Cassandro C., Albera R. Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media. Int J Gen Med. 2012;5:991–997. https://doi.org/10.2147/IJGM.S38859.Wilcox C.R., Stuart B., Leaver H., Lown M., Willcox M. et al. Effectiveness of the probiotic Streptococcus salivarius K12 for the treatment and/or prevention of sore throat: a systematic review. Clin Microbiol Infect. 2019;25(6):673–680. https://doi.org/10.1016/j.cmi.2018.12.031.Wilcox C.R., Stuart B., Leaver H., Lown M., Willcox M. et al. Effectiveness of the probiotic Streptococcus salivarius K12 for the treatment and/or prevention of sore throat: a systematic review. Clin Microbiol Infect. 2019;25(6):673–680. https://doi.org/10.1016/j.cmi.2018.12.031.Дайхес Н.А., Баранов А.А., Лобзин Ю.В., Намазова-Баранова Л.С., Козлов Р.С., Поляков Д.П. и др. Острый тонзиллит и фарингит (Острый тонзиллофарингит): клинические рекомендации. М.; 2021. 51 с. Режим доступа: https://cr.minzdrav.gov.ru/recomend/306_2.Daikhes N.A., Baranov A.A., Lobzin Yu.V., Namazova-Baranova L.S., Kozlov R.S., Polyakov D.P. et al. Acute tonsillitis and pharyngitis (Acute tonsillopharyngitis): clinical guidelines. Moscow; 2021. 51 p. (In Russ.) Available at: https://cr.minzdrav.gov.ru/recomend/306_2.

The authors declare that there are no conflicts of interest present.