medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2019-17-236-242medsovet-4827Research ArticleШкола педиатраSchool for pediatricianПробиотик Lactobacillus reuteri DSM 17938: что известно о нем сегодня?Probiotic Lactobacillus reuteri DSM 17938: what is known about it today?https://orcid.org/0000-0003-4200-4598ЗахароваИ. Н.ZakharovaI. N.

Захарова Ирина Николаевна, доктор медицинских наук, профессор, заслуженный врач России, заведующая кафедрой педиатрии с курсом поликлинической педиатрии им. Г.Н. Сперанского

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Irina N. Zakharova, Dr. of Sci. (Med), Professor, Honoured Doctor of Russia, Head of Speranskiy Chair for Paediatrics with Polyclinic Paediatrics Module

b. 1, 2/1, Barrikadnaya St., Moscow, 125993

kafedra25@yandex.ruБережнаяИ. В.BerezhnayaI. V.

Бережная Ирина Владимировна, кандидат медицинских наук, доцент кафедры педиатрии с курсом поликлинической педиатрии им. Г.Н. Сперанского

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Irina V. Berezhnaya, Cand. of Sci. (Med), District Children’s Gastroenterologist for Northwest Administrative District of Moscow, Assistant Professor of Speranskiy Chair for Paediatrics with Polyclinic Paediatrics Module

b. 1, 2/1, Barrikadnaya St., Moscow, 125993

berezhnaya-irina26@yandex.ruКучинаА. Е.KuchinaA. Е.

Кучина Анастасия Евгеньевна, врач-педиатр, аспирант кафедры педиатрии с курсом поликлинической педиатрии им. Г.Н. Сперанского

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Anastasiya E. Kuchina, Pediatrician, postgraduate student, G.N. Speransky Chair for Paediatrics with Polyclinic Paediatrics Module

b. 1, 2/1, Barrikadnaya St., Moscow, 125993

kafedra25@yandex.ruДедиковаО. В.DedikovaO. V.

Дедикова Ольга Валерьевна, менеджер по развитию педиатрического направления представительства АО «Дельта Медикел Промоушнз АГ» в РФ

125993, Москва, ул. Баррикадная, д. 2/1, стр.,

123001, Москва, Трехпрудный пер., д .4, стр. 1

Ol’ga V. Dedikova, Manager for Pediatric Development of the Representative Office of Delta Medical Promotion AG in Russia

b. 1, 2/1, Barrikadnaya St., Moscow, 125993

b.1, 4, Tryokhprudny Lane, Moscow, 123001

olga.dedikova@deltaswiss.euРоссийская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuing Postgraduate EducationRussian FederationРоссийская медицинская академия непрерывного профессионального образования; Представительство АО «Дельта Медикел Промоушнз АГ» в РФРоссияRussian Medical Academy of Continuing Postgraduate Education; Representative Office of Delta Medical Promotion AG in RussiaRussian Federation201924112019017236242Copyright © Захарова И.Н., Бережная И.В., Кучина А.Е., Дедикова О.В., 20192019Захарова И.Н., Бережная И.В., Кучина А.Е., Дедикова О.В.Zakharova I.N., Berezhnaya I.V., Kuchina A.Е., Dedikova O.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/4827

Обзор посвящен анализу данных об эффектах Lactobacillus reuteri DSM 17938, получивших подтверждение в клинических исследованиях. Благодаря своей антимикробной активности L. reuteri способны ингибировать колонизацию патогенными микроорганизмами и восстанавливать состав комменсальной микробиоты кишечника. Другое исследование показало положительный защитный эффект микробиоты кишечника при приеме L. reuteri одновременно с антибиотиками. Кроме того, L. reuteri поддерживает функционирование иммунной системы организма человека. Например, некоторые штаммы L. reuteri могут снижать выработку провоспалительных цитокинов, одновременно стимулируя развитие и пролиферацию регуляторных Т-лимфоцитов. Добавление в пищу L. reuteri может быть привлекательным с точки зрения предотвращения развития воспалительных заболеваний кишечника. Результаты недавнего метаанализа подтвердили эффективность L. reuteri в терапии младенческих колик. Дальнейшие исследования направлены на поиск доказательств эффективности применения L. reuteri у детей, находящихся на искусственном вскармливании, с младенческими коликами и у детей, рожденных путем кесарева сечения.

The review is devoted to the analysis of data on the effects of Lactobacillus reuteri DSM 17938, confirmed in clinical trials. Thanks to their antimicrobial activity, L. reuteri is able to inhibit colonization by pathogenic microorganisms and restore the composition of compensatory intestinal microbiota. Another study showed a positive protective effect of intestinal microbiota when administered L. reuteri simultaneously with antibiotics. In addition, L. reuteri supports the immune system of the human body. For example, some strains of L. reuteri may reduce the production of pro-inflammatory cytokines while stimulating the development and proliferation of regulatory T-lymphocytes. Adding L. reuteri to the diet may be attractive in terms of preventing the development of inflammatory bowel disease. The results of a recent meta-analysis confirmed the efficacy of L. reuteri in the treatment of infantile colic. Further research is aimed at finding evidence of the efficacy of L. reuteri use in children who are artificially fed, with infant colic and in children born by caesarean section.

лактобацилла ройтеридетипробиотикмладенческие коликимикробиотаиммунная системавоспалительные заболеванияКЖКкесарево сечениеLactobacillus reuterichildrenprobioticinfant colicmicrobiotaimmune systeminflammatory diseasesSCFACaesarean sectionReferencesWorld Gastroenterology Organisation Global Guidelines: Celiac Disease February 2017. doi: 10.1097/MCG.0000000000000919.World Gastroenterology Organisation Global Guidelines: Celiac Disease February 2017. doi: 10.1097/MCG.0000000000000919.Oh P.L., Benson A.K., Peterson D.A., Patil P.B., Moriyama E.N., Roos S., Walter J. Diversification of the gut symbiont Lactobacillus reuteri as a result of host-driven evolution. ISME J. 2010;4:377–387. doi: 10.1038/ismej.2009.123.Oh P.L., Benson A.K., Peterson D.A., Patil P.B., Moriyama E.N., Roos S., Walter J. Diversification of the gut symbiont Lactobacillus reuteri as a result of host-driven evolution. ISME J. 2010;4:377–387. doi: 10.1038/ismej.2009.123.Walter J., Britton R.A., Roos S. Host-microbial symbiosis in the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm. Proc. Natl. Acad. Sci. U.S.A. 2011;108 (Suppl. 1):4645–4652. doi. 10.1073/pnas.1000099107.Walter J., Britton R.A., Roos S. Host-microbial symbiosis in the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm. Proc. Natl. Acad. Sci. U.S.A. 2011;108 (Suppl. 1):4645–4652. doi. 10.1073/pnas.1000099107.Valeur N., Engel P. Carbajal N., Connolly E., Ladefoged K. Colonization and immunomodulation by Lactobacillus reuteri ATCC 55730 in the human gastrointestinal tract. Appl Environ Microbiol. 2004;70;1176–1181. doi: 10.1128/aem.70.2.1176-1181.2004.Valeur N., Engel P. Carbajal N., Connolly E., Ladefoged K. Colonization and immunomodulation by Lactobacillus reuteri ATCC 55730 in the human gastrointestinal tract. Appl Environ Microbiol. 2004;70;1176–1181. doi: 10.1128/aem.70.2.1176-1181.2004.Bjorkman P. Colonization of the human gastrointestinal tract by the lactic acid bacteria Lactobacillus reuteri. M.Sc. thesis, Dept. of Food Technology, University of Helsinki, Finland. 1999. Available at: https://www.biogaia.com/study/colonization-of-the-human-gastrointestinaltractby-lactobacillus-reuteri/.Bjorkman P. Colonization of the human gastrointestinal tract by the lactic acid bacteria Lactobacillus reuteri. M.Sc. thesis, Dept. of Food Technology, University of Helsinki, Finland. 1999. Available at: https://www.biogaia.com/study/colonization-of-the-human-gastrointestinaltractby-lactobacillus-reuteri/.Sinkiewicz G., Nordstrom E.A. Occurrence of Lactobacillus reuteri, lactobacilli and bifidobacteria in human breast milk. Pediatric Research. 2005;58:415. doi. 10.1080/0891060080234100.Sinkiewicz G., Nordstrom E.A. Occurrence of Lactobacillus reuteri, lactobacilli and bifidobacteria in human breast milk. Pediatric Research. 2005;58:415. doi. 10.1080/0891060080234100.Krumbeck J.A., Marsteller N.L., Frese S.A., Peterson D.A., Ramer-Tait A.E., Hutkins R.W., Walter J. Characterization of the ecological role of genes mediating acid resistance in Lactobacillus reuteri during colonization of the gastrointestinal tract. Environ Microbiol. 2016;18:2172–2184. doi: 10.1111/1462-2920.13108.Krumbeck J.A., Marsteller N.L., Frese S.A., Peterson D.A., Ramer-Tait A.E., Hutkins R.W., Walter J. Characterization of the ecological role of genes mediating acid resistance in Lactobacillus reuteri during colonization of the gastrointestinal tract. Environ Microbiol. 2016;18:2172–2184. doi: 10.1111/1462-2920.13108.Seo B. J., Mun M. R., J RK., Kim C. J., Lee I., Chang Y. H., Park Y.H. Bile tolerant Lactobacillus reuteri isolated from pig feces inhibits enteric bacterial pathogens and porcine rotavirus. Vet. Res. Commun. 2010;34:323–333. doi: 10.1007/s11259-010-9357-6.Seo B. J., Mun M. R., J RK., Kim C. J., Lee I., Chang Y. H., Park Y.H. Bile tolerant Lactobacillus reuteri isolated from pig feces inhibits enteric bacterial pathogens and porcine rotavirus. Vet. Res. Commun. 2010;34:323–333. doi: 10.1007/s11259-010-9357-6.Sarxelin M., Tynkkynen S., Mattila-sandholm T., Vos W.M. Probiotic and other functional microbes: From markets to mechanisms. Curr. Opin. Microbiol. 2005;16:204–211. doi: 10.1016/j.copbio.2005.02.003.Sarxelin M., Tynkkynen S., Mattila-sandholm T., Vos W.M. Probiotic and other functional microbes: From markets to mechanisms. Curr. Opin. Microbiol. 2005;16:204–211. doi: 10.1016/j.copbio.2005.02.003.Lewis K. Riddle of biofilm resistance. Antimicrob. Agents Chemother. 2001;45:999– 1007. doi: 10.1128/AAC.45.4.999-1007.2001.Lewis K. Riddle of biofilm resistance. Antimicrob. Agents Chemother. 2001;45:999– 1007. doi: 10.1128/AAC.45.4.999-1007.2001.Roos S., Jonsson H. A high-molecular-mass cellsurface protein from Lactobacillus reuteri 1063 adheres to mucus components. Microbiology. 2002;148(Pt 2):433–442. doi: 10.1099/00221287148-2-433.Roos S., Jonsson H. A high-molecular-mass cellsurface protein from Lactobacillus reuteri 1063 adheres to mucus components. Microbiology. 2002;148(Pt 2):433–442. doi: 10.1099/00221287148-2-433.Kleerebezem M., Hols P., Bernard E., Rolain T., Zhou M., Siezen R. J., P.A. Bron. The extracellular biology of the lactobacilli. FEMS Microbiol. Rev. 2010;34:199–230. doi: 10.1111/j.1574-6976.2009.00208.x.Kleerebezem M., Hols P., Bernard E., Rolain T., Zhou M., Siezen R. J., P.A. Bron. The extracellular biology of the lactobacilli. FEMS Microbiol. Rev. 2010;34:199–230. doi: 10.1111/j.1574-6976.2009.00208.x.Gunning A.P., Kavanaugh D., Thursby E., Etzold S., MacKenzie D.A., Juge N. Use of atomic force microscopy to study the multi-modular interaction of bacterial adhesins to mucins. Int. J. Mol. Sci. 2016;17:1854. doi: 10.3390/ijms17111854.Gunning A.P., Kavanaugh D., Thursby E., Etzold S., MacKenzie D.A., Juge N. Use of atomic force microscopy to study the multi-modular interaction of bacterial adhesins to mucins. Int. J. Mol. Sci. 2016;17:1854. doi: 10.3390/ijms17111854.Mackenzie D. A., Jeffers F., Parker M. L., VibertVallet A., Bongaerts R. J., Roos S., Walter J., Juge N. Strain-specific diversity of mucus-binding proteins in the adhesion and aggregation properties of Lactobacillus reuteri. Microbiology. 2010;156(11):3368–3378. doi: 10.1099/mic.0.043265-0.Mackenzie D. A., Jeffers F., Parker M. L., VibertVallet A., Bongaerts R. J., Roos S., Walter J., Juge N. Strain-specific diversity of mucus-binding proteins in the adhesion and aggregation properties of Lactobacillus reuteri. Microbiology. 2010;156(11):3368–3378. doi: 10.1099/mic.0.043265-0.Mu Q., Tavella V.J., Luo X.M. Role of Lactobacillus reuteri in Human Health and Diseases. Front. Microbiol. 2018. doi. 10.3389/fmicb.2018.00757.Mu Q., Tavella V.J., Luo X.M. Role of Lactobacillus reuteri in Human Health and Diseases. Front. Microbiol. 2018. doi. 10.3389/fmicb.2018.00757.Navarro J.B., Mashburn-Warren L., Bakaletz L.O., Bailey M.T., Goodman S.D. Enhanced probiotic potential of Lactobacillus reuteri when delivered as a biofilm on dextranomer microspheres that contain beneficial cargo. Front. Microbiol. 2017;8:489. doi: 10.3389/fmicb.2017.00489.Navarro J.B., Mashburn-Warren L., Bakaletz L.O., Bailey M.T., Goodman S.D. Enhanced probiotic potential of Lactobacillus reuteri when delivered as a biofilm on dextranomer microspheres that contain beneficial cargo. Front. Microbiol. 2017;8:489. doi: 10.3389/fmicb.2017.00489.Dobrogosz W.J., Casas I.A., Pagano G.A., Talarico T.L., Sjoberg B-M., Karlsson M. Lactobacillus reuteri and the enteric microbiota. In: The Regulatory and Protective Role of the Normal Microflora. 1989;283–292. Eds.: Grubb R., Midtvedt T., Norin E.Macmillian LTD, London.Dobrogosz W.J., Casas I.A., Pagano G.A., Talarico T.L., Sjoberg B-M., Karlsson M. Lactobacillus reuteri and the enteric microbiota. In: The Regulatory and Protective Role of the Normal Microflora. 1989;283–292. Eds.: Grubb R., Midtvedt T., Norin E.Macmillian LTD, London.Cadieux P., Wind A., Sommer P., Schaefer L., Crowley K., Britton R. A., G. Reid. Evaluation of reuterin production in urogenital probiotic Lactobacillus reuteri RC-14. Appl. Environ. Microbiol. 2008;74:4645–4649. doi: 10.1128/AEM.00139-08.Cadieux P., Wind A., Sommer P., Schaefer L., Crowley K., Britton R. A., G. Reid. Evaluation of reuterin production in urogenital probiotic Lactobacillus reuteri RC-14. Appl. Environ. Microbiol. 2008;74:4645–4649. doi: 10.1128/AEM.00139-08.Wu R.Y. Lactobacillus: A probiotic modulator of gastrointestinal motility. Meducator. 2011;19:16-18.Wu R.Y. Lactobacillus: A probiotic modulator of gastrointestinal motility. Meducator. 2011;19:16-18.Casas I.A., Dobrogosz W.J. Validation of the probiotic concept: Lactobacillus reuteri confers broad-spectrum protection against disease in humans and animals. Microbial Ecol Health Dis. 2000;12(4):247– 285. doi: 10.1080/08910600050216246-1.Casas I.A., Dobrogosz W.J. Validation of the probiotic concept: Lactobacillus reuteri confers broad-spectrum protection against disease in humans and animals. Microbial Ecol Health Dis. 2000;12(4):247– 285. doi: 10.1080/08910600050216246-1.Reuter G. The Lactobacillus and Bifidobacterium microflora of the human intestine: composition and succession. Curr Issues Intest Microbiol. 2001;2:43-53. Available at: https://www.ncbi.nlm.nih.gov/pubmed/11721280.Reuter G. The Lactobacillus and Bifidobacterium microflora of the human intestine: composition and succession. Curr Issues Intest Microbiol. 2001;2:43-53. Available at: https://www.ncbi.nlm.nih.gov/pubmed/11721280.Axelsson L., Chung T.C., Dobrogosz W., Lindgren S.E. Production of a broad spectrum antimicrobial substance by Lactobacillus reuteri. Microb Ecol health Dis. 1989;2:131–136. doi: 10.3109/08910608909140210.Axelsson L., Chung T.C., Dobrogosz W., Lindgren S.E. Production of a broad spectrum antimicrobial substance by Lactobacillus reuteri. Microb Ecol health Dis. 1989;2:131–136. doi: 10.3109/08910608909140210.Luo H., Zhou D., Liu X., Nie Z., Quiroga-Sanchez D.L., Chang Y. Production of 3-Hydroxypropionic Acid via the Propionyl-CoA Pathway Using Recombinant Escherichia coli Strains. PLOS ONE. 2016;1-13. doi: 10.1371/journal.pone.0156286.Luo H., Zhou D., Liu X., Nie Z., Quiroga-Sanchez D.L., Chang Y. Production of 3-Hydroxypropionic Acid via the Propionyl-CoA Pathway Using Recombinant Escherichia coli Strains. PLOS ONE. 2016;1-13. doi: 10.1371/journal.pone.0156286.Sebastianes F.L.S., Cabedo N., El Aouad N., Valente A.M.M. P., Lacava P.T., Azevedo J.L., Pizzirani-Kleiner A.A., Cortes D. 3-Hydroxypropionic acid as an antibacterial agent from endophytic fungi Diaporthe phaseolorum. Curr. Microbiol. 2012;65:622–632. doi: 10.1007/s00284-012-0206-4.Sebastianes F.L.S., Cabedo N., El Aouad N., Valente A.M.M. P., Lacava P.T., Azevedo J.L., Pizzirani-Kleiner A.A., Cortes D. 3-Hydroxypropionic acid as an antibacterial agent from endophytic fungi Diaporthe phaseolorum. Curr. Microbiol. 2012;65:622–632. doi: 10.1007/s00284-012-0206-4.Stevens J. F., Maier C. S. Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol. Nutr. Food Res. 2008;52:7–25. doi: 10.1002/mnfr.200700412.Stevens J. F., Maier C. S. Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol. Nutr. Food Res. 2008;52:7–25. doi: 10.1002/mnfr.200700412.Engels C., Schwab C., Zhang J., Stevens M. J., Bieri C., Ebert M. O., McNeill K., Sturla S.J., Lacroix C. Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin. Sci. Rep. 2016;6:36246. doi: 10.1038/srep36246.Engels C., Schwab C., Zhang J., Stevens M. J., Bieri C., Ebert M. O., McNeill K., Sturla S.J., Lacroix C. Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin. Sci. Rep. 2016;6:36246. doi: 10.1038/srep36246.Mishra S. K., Malik R. K., Manju G., Pandey N., Singroha G., Behare P. et al. Characterization of a reuterin-producing Lactobacillus reuteri BPL-36 strain isolated from human infant fecal sample. Probiotics Antimicrob Proteins. 2012;4:154–161. doi: 10.1007/s12602-012-9103-1.Mishra S. K., Malik R. K., Manju G., Pandey N., Singroha G., Behare P. et al. Characterization of a reuterin-producing Lactobacillus reuteri BPL-36 strain isolated from human infant fecal sample. Probiotics Antimicrob Proteins. 2012;4:154–161. doi: 10.1007/s12602-012-9103-1.Ganzle M. G., Vogel R. F. Studies on the mode of action of reutericyclin. Appl. Environ. Microbiol. 2003;69:1305–1307. doi: 10.1128/AEM.69.2.1305-1307.2003.Ganzle M. G., Vogel R. F. Studies on the mode of action of reutericyclin. Appl. Environ. Microbiol. 2003;69:1305–1307. doi: 10.1128/AEM.69.2.1305-1307.2003.Burge G., Saulou-Berion C., Moussa M., Pollet B., Flourat A., Allais F. et al. Diversity of Lactobacillus reuteri strains in converting glycerol into 3-hydroxypropionic acid. Appl. Biochem. Biotechnol. 2015;177:923–939. doi: 10.1007/s12010-015-1787-8.Burge G., Saulou-Berion C., Moussa M., Pollet B., Flourat A., Allais F. et al. Diversity of Lactobacillus reuteri strains in converting glycerol into 3-hydroxypropionic acid. Appl. Biochem. Biotechnol. 2015;177:923–939. doi: 10.1007/s12010-015-1787-8.Gopi G.R., Ganesh N., Pandiaraj S., Sowmiya B., Brajesh R.G., Ramalingam S. A study on enhanced expression of 3-hydroxypropionic acid pathway genes and impact on its production in Lactobacillus reuteri. Food Technol. Biotechnol. 2015;53:331–336. doi: 10.17113/ftb.53.03.15.3976.Gopi G.R., Ganesh N., Pandiaraj S., Sowmiya B., Brajesh R.G., Ramalingam S. A study on enhanced expression of 3-hydroxypropionic acid pathway genes and impact on its production in Lactobacillus reuteri. Food Technol. Biotechnol. 2015;53:331–336. doi: 10.17113/ftb.53.03.15.3976.Jiang X., Meng X., Xian M. Biosynthetic pathways for 3-hydroxypropionic acid production. Applied Microbiology and Biotechnology. 2009;82(6):995– 1003. doi: 10.1007/s00253-009-1898-7.Jiang X., Meng X., Xian M. Biosynthetic pathways for 3-hydroxypropionic acid production. Applied Microbiology and Biotechnology. 2009;82(6):995– 1003. doi: 10.1007/s00253-009-1898-7.Zhang D., Hillmyer M. A., Tolman W. B. A new synthetic route to poly [3-hydroxypropionic acid] (P[3-HP]): ring-opening polymerization of 3-HP macrocyclic esters. Macromol. 2004;37:8198–8200. doi: 10.1021/ma048092q.Zhang D., Hillmyer M. A., Tolman W. B. A new synthetic route to poly [3-hydroxypropionic acid] (P[3-HP]): ring-opening polymerization of 3-HP macrocyclic esters. Macromol. 2004;37:8198–8200. doi: 10.1021/ma048092q.Sardari R. R. R., Dishisha T., Pyo S. H., Hatti-Kaul R. Improved production of 3-hydroxypropionaldehyde by complex formation with bisulfite during bio-transformation of glycerol. Biotechnol. Bioeng. 2013;110:1243–1248. doi: 10.1002/bit.24787.Sardari R. R. R., Dishisha T., Pyo S. H., Hatti-Kaul R. Improved production of 3-hydroxypropionaldehyde by complex formation with bisulfite during bio-transformation of glycerol. Biotechnol. Bioeng. 2013;110:1243–1248. doi: 10.1002/bit.24787.Sardari R.R.R., Dishisha T., Pyo S.H., Hatti-Kaul R. Biotransformation of glycerol to 3-hydroxypropionaldehyde: Improved production by in situ complexation with bisulfate in a fed-batch mode and separation on anion exchanger. J. Biotechnol. 2013;168:534–542. doi: 10.1016/j.jbiotec.2013.09.009.Sardari R.R.R., Dishisha T., Pyo S.H., Hatti-Kaul R. Biotransformation of glycerol to 3-hydroxypropionaldehyde: Improved production by in situ complexation with bisulfate in a fed-batch mode and separation on anion exchanger. J. Biotechnol. 2013;168:534–542. doi: 10.1016/j.jbiotec.2013.09.009.Cherian P.T., Wu X., Yang L., Scarborough J.S., Singh A.P., Alam Z.A. et al. Gastrointestinal localization of metronidazole by a lactobacilliinspired tetramic acid motif improves treatment outcomes in the hamster model of Clostridium difficile infection. J. Antimicrob. Chemother. 2015;70:3061–3069. doi: 10.1093/jac/dkv231.Cherian P.T., Wu X., Yang L., Scarborough J.S., Singh A.P., Alam Z.A. et al. Gastrointestinal localization of metronidazole by a lactobacilliinspired tetramic acid motif improves treatment outcomes in the hamster model of Clostridium difficile infection. J. Antimicrob. Chemother. 2015;70:3061–3069. doi: 10.1093/jac/dkv231.Abhisingha M., Dumnil J., Pitaksutheepong C. Selection of potential probiotic Lactobacillus with inhibitory activity against Salmonella and fecal coliform bacteria. Probiotics Antimicrob. Proteins. 2018;10(2):218-227. doi: 10.1007/s12602-017-9304-8.Abhisingha M., Dumnil J., Pitaksutheepong C. Selection of potential probiotic Lactobacillus with inhibitory activity against Salmonella and fecal coliform bacteria. Probiotics Antimicrob. Proteins. 2018;10(2):218-227. doi: 10.1007/s12602-017-9304-8.Genis S., Sanchez-Chardi A., Bach A., Fabregas F., Aris A. A combination of lactic acid bacteria regulates Escherichia coli infection and inflammation of the bovine endometrium. J. Dairy Sci. 2017;100:479–492. doi: 10.3168/jds.2016-11671.Genis S., Sanchez-Chardi A., Bach A., Fabregas F., Aris A. A combination of lactic acid bacteria regulates Escherichia coli infection and inflammation of the bovine endometrium. J. Dairy Sci. 2017;100:479–492. doi: 10.3168/jds.2016-11671.Shornikova A.V., Casas I.A., Isolauri E., Mykkanen H., Vesikari T. Lactobacillus reuteri as a therapeutic agent in acute diarrhea in young children. J. Pediatr. Gastroenterol. Nutr. 1997;24:399– 404. doi: 10.1097/00005176-199704000-00008.Shornikova A.V., Casas I.A., Isolauri E., Mykkanen H., Vesikari T. Lactobacillus reuteri as a therapeutic agent in acute diarrhea in young children. J. Pediatr. Gastroenterol. Nutr. 1997;24:399– 404. doi: 10.1097/00005176-199704000-00008.Preidis G.A., Saulnier D.M., Blutt S.E., Mistretta T.A., Riehle, K.P., Major, A.M. et al. Host response to probiotics determined by nutritional status of rotavirus-infected neonatal mice. J. Pediatr. Gastroenterol. Nutr. 2012;55:299–307. doi: 10.1097/MPG.0b013e31824d2548.Preidis G.A., Saulnier D.M., Blutt S.E., Mistretta T.A., Riehle, K.P., Major, A.M. et al. Host response to probiotics determined by nutritional status of rotavirus-infected neonatal mice. J. Pediatr. Gastroenterol. Nutr. 2012;55:299–307. doi: 10.1097/MPG.0b013e31824d2548.Ang L.Y., Too H.K., Tan E.L., Chow T.K., Shek P.C., Tham E. et al. Antiviral activity of Lactobacillus reuteri Protectis against Coxsackievirus A and Enterovirus 71 infection in human skeletal muscle and colon cell lines. Virol. J. 2016;13:111. doi: 10.1186/s12985-016-0567-6.Ang L.Y., Too H.K., Tan E.L., Chow T.K., Shek P.C., Tham E. et al. Antiviral activity of Lactobacillus reuteri Protectis against Coxsackievirus A and Enterovirus 71 infection in human skeletal muscle and colon cell lines. Virol. J. 2016;13:111. doi: 10.1186/s12985-016-0567-6.Diaz M., Ladero V., del Rio B., Redruello B., Fernandez M., Martin M.C. et al. Biofilm-forming capacity in biogenic amine-producing bacteria isolated from dairy products. Front. Microbiol. 2016;7:591. doi: 10.3389/fmicb.2016.00591.Diaz M., Ladero V., del Rio B., Redruello B., Fernandez M., Martin M.C. et al. Biofilm-forming capacity in biogenic amine-producing bacteria isolated from dairy products. Front. Microbiol. 2016;7:591. doi: 10.3389/fmicb.2016.00591.Greifova G., Majekova H., Greif G., Body P., Greifova M., Dubnickova M. Analysis of antimicrobial and immunomodulatory substances produced by heterofermentative Lactobacillus reuteri. Folia Microbiol. 2017;62:515–524. doi: 10.1007/s12223-017-0524-9.Greifova G., Majekova H., Greif G., Body P., Greifova M., Dubnickova M. Analysis of antimicrobial and immunomodulatory substances produced by heterofermentative Lactobacillus reuteri. Folia Microbiol. 2017;62:515–524. doi: 10.1007/s12223-017-0524-9.Thomas C. M., Hong T., van Pijkeren J. P., Hemarajata P., Trinh D.V., Hu W. et al. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One. 2012;7:31951. doi: 10.1371/journal.pone.0031951.Thomas C. M., Hong T., van Pijkeren J. P., Hemarajata P., Trinh D.V., Hu W. et al. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One. 2012;7:31951. doi: 10.1371/journal.pone.0031951.Rossi F., Gardini F., Rizzotti L., La Gioia F., Tabanelli G., and Torriani S. Quantitative analysis of histidine decarboxylase gene (hdcA) transcription and histamine production by Streptococcus thermophilus PRI60 under conditions relevant to cheese making. Appl. Environ. Microbiol. 2011;77:2817–2822. doi: 10.1128/AEM.02531-10.Rossi F., Gardini F., Rizzotti L., La Gioia F., Tabanelli G., and Torriani S. Quantitative analysis of histidine decarboxylase gene (hdcA) transcription and histamine production by Streptococcus thermophilus PRI60 under conditions relevant to cheese making. Appl. Environ. Microbiol. 2011;77:2817–2822. doi: 10.1128/AEM.02531-10.Gao C., Major A., Rendon D., Lugo M., Jackson V., Shi Z. et al. Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri. mBio. 2015;6:01358-15. doi: 10.1128/mBio.01358-15.Gao C., Major A., Rendon D., Lugo M., Jackson V., Shi Z. et al. Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri. mBio. 2015;6:01358-15. doi: 10.1128/mBio.01358-15.Thomas C.M., Saulnier D.M., Spinler J.K., Hemarajata P., Gao C., Jones S.E. et al. FolC2mediated folate metabolism contributes to suppression of inflammation by probiotic Lactobacillus reuteri. Microbiologyopen. 2016;5:802–818. doi: 10.1002/mbo3.371.Thomas C.M., Saulnier D.M., Spinler J.K., Hemarajata P., Gao C., Jones S.E. et al. FolC2mediated folate metabolism contributes to suppression of inflammation by probiotic Lactobacillus reuteri. Microbiologyopen. 2016;5:802–818. doi: 10.1002/mbo3.371.Hemarajata P., Gao C., Pflughoeft K.J., Thomas C.M., Saulnier D.M., Spinler J.K. et al. Lactobacillus reuteri-specific immunoregulatory gene rsiR modulates histamine production and immunomodulation by Lactobacillus reuteri. J. Bacteriol. 2013;195:5567–5576. doi: 10.1128/JB.00261-13.Hemarajata P., Gao C., Pflughoeft K.J., Thomas C.M., Saulnier D.M., Spinler J.K. et al. Lactobacillus reuteri-specific immunoregulatory gene rsiR modulates histamine production and immunomodulation by Lactobacillus reuteri. J. Bacteriol. 2013;195:5567–5576. doi: 10.1128/JB.00261-13.Linares D.M., Gomez C., Renes E., Fresno J. M., Tornadijo M. E., Ross R.P. et al. Lactic acid bacteria and bifidobacteria with potential to design natural biofunctional health-promoting dairy foods. Front. Microbiol. 2017;8:846. doi: 10.3389/fmicb.2017.00846.Linares D.M., Gomez C., Renes E., Fresno J. M., Tornadijo M. E., Ross R.P. et al. Lactic acid bacteria and bifidobacteria with potential to design natural biofunctional health-promoting dairy foods. Front. Microbiol. 2017;8:846. doi: 10.3389/fmicb.2017.00846.Morita H., Toh H., Fukuda S., Horikawa H., Oshima K., Suzuki T. et al. Comparative genome analysis of Lactobacillus reuteri and Lactobacillus fermentum reveal a genomic island for reuterin and cobalamin production. DNA Res. 2008;15:151– 161. doi: 10.1093/dnares/dsn009.Morita H., Toh H., Fukuda S., Horikawa H., Oshima K., Suzuki T. et al. Comparative genome analysis of Lactobacillus reuteri and Lactobacillus fermentum reveal a genomic island for reuterin and cobalamin production. DNA Res. 2008;15:151– 161. doi: 10.1093/dnares/dsn009.Santos F., Spinler J.K., Saulnier D.M., Molenaar D., Teusink B., de Vos W. M. et al. Functional identification in Lactobacillus reuteri of a PocR-like transcription factor regulating glycerol utilization and vitamin B12 synthesis. Microb. Cell Fact. 2011;10:55. doi: 10.1186/1475-2859-10-55.Santos F., Spinler J.K., Saulnier D.M., Molenaar D., Teusink B., de Vos W. M. et al. Functional identification in Lactobacillus reuteri of a PocR-like transcription factor regulating glycerol utilization and vitamin B12 synthesis. Microb. Cell Fact. 2011;10:55. doi: 10.1186/1475-2859-10-55.Molina V. C., Medici M., Taranto M. P., Font de Valdez G. Lactobacillus reuteri CRL 1098 prevents side effects produced by a nutritional vitamin B deficiency. J. Appl.Microbiol. 2009;106:467–473. doi: 10.1111/j.1365-2672.2008.04014.x.Molina V. C., Medici M., Taranto M. P., Font de Valdez G. Lactobacillus reuteri CRL 1098 prevents side effects produced by a nutritional vitamin B deficiency. J. Appl.Microbiol. 2009;106:467–473. doi: 10.1111/j.1365-2672.2008.04014.x.Santos F., Wegkamp A., de Vos W. M., Smid E. J., Hugenholtz J. High-Level folate production in fermented foods by the B12 producer Lactobacillus reuteri JCM11. Environ. Microbiol. 2008;74:3291– 3294. doi: 10.1128/AEM.02719-07.Santos F., Wegkamp A., de Vos W. M., Smid E. J., Hugenholtz J. High-Level folate production in fermented foods by the B12 producer Lactobacillus reuteri JCM11. Environ. Microbiol. 2008;74:3291– 3294. doi: 10.1128/AEM.02719-07.Inoue K., Shirai T., Ochiai H., Kasao M., Hayakawa K., Kimura M. et al. Blood-pressurelowering effect of a novel fermented milk containing γ-aminobutyric acid (GABA) in mild hypertensives. Eur. J. Clin. Nutr. 2003;57:490– 495. doi: 10.1038/sj.ejcn.1601555.Inoue K., Shirai T., Ochiai H., Kasao M., Hayakawa K., Kimura M. et al. Blood-pressurelowering effect of a novel fermented milk containing γ-aminobutyric acid (GABA) in mild hypertensives. Eur. J. Clin. Nutr. 2003;57:490– 495. doi: 10.1038/sj.ejcn.1601555.Marques T.M., Patterson E., Wall R., O’Sullivan O., Fitzgerald G.F., Cotter P.D. et al. Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model. Benef. Microbes. 2016;7:409–420. doi: 10.3920/BM2015.0154.Marques T.M., Patterson E., Wall R., O’Sullivan O., Fitzgerald G.F., Cotter P.D. et al. Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model. Benef. Microbes. 2016;7:409–420. doi: 10.3920/BM2015.0154.Foster A.C., Kemp J.A. Glutamateand GABAbased CNS therapeutics. Curr. Opin. Pharmacol. 2006;6:7–17. doi: 10.1016/j.coph.2005.11.005.Foster A.C., Kemp J.A. Glutamateand GABAbased CNS therapeutics. Curr. Opin. Pharmacol. 2006;6:7–17. doi: 10.1016/j.coph.2005.11.005.Chen L., Zhao H., Zhang C., Lu Y., Zhu X., Lu Z. γ-Aminobutyric acid-rich yogurt fermented by Streptococcus salivarius subsp. thermophiles fmb5 appears to have anti-diabetic effect on streptozotocininduced diabetic mice. J. Func. Foods. 2016;20:267–275. doi: 10.1016/j.jff.2015.10.030.Chen L., Zhao H., Zhang C., Lu Y., Zhu X., Lu Z. γ-Aminobutyric acid-rich yogurt fermented by Streptococcus salivarius subsp. thermophiles fmb5 appears to have anti-diabetic effect on streptozotocininduced diabetic mice. J. Func. Foods. 2016;20:267–275. doi: 10.1016/j.jff.2015.10.030.Pouliot-Mathieu K., Gardner-Fortier C., Lemieux S., St-Gelais D., Champagne C.P., Vuillemard J.C. Effect of cheese containing gamma-aminobutyric acid-producing lactic acid bacteria on blood pressure in men. PharmaNutrition. 2013;1:141–148. doi: 10.1016/j.phanu.2013.06.003.Pouliot-Mathieu K., Gardner-Fortier C., Lemieux S., St-Gelais D., Champagne C.P., Vuillemard J.C. Effect of cheese containing gamma-aminobutyric acid-producing lactic acid bacteria on blood pressure in men. PharmaNutrition. 2013;1:141–148. doi: 10.1016/j.phanu.2013.06.003.Romeo M.G., Romeo D.M., Trovato L., Oliveri S., Palermo F., Cota F., Betta P. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome. Journal of Perinatology. 2011;31:63–69. doi: 10.1038/jp.2010.57.Romeo M.G., Romeo D.M., Trovato L., Oliveri S., Palermo F., Cota F., Betta P. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome. Journal of Perinatology. 2011;31:63–69. doi: 10.1038/jp.2010.57.Savino F., Cordisco L., Tarasco V., Palumeri E., Calabrese R., Oggero R., Roos S., Matteuzzi D. Lactobacillus reuteri DSM 17938 in Infantile Colic: A Randomized, Double-Blind, PlaceboControlled Trial. Pediatrics. 2010;126;e526-e533. doi: https://doi.org/10.1542/peds.2010-0433.Savino F., Cordisco L., Tarasco V., Palumeri E., Calabrese R., Oggero R., Roos S., Matteuzzi D. Lactobacillus reuteri DSM 17938 in Infantile Colic: A Randomized, Double-Blind, PlaceboControlled Trial. Pediatrics. 2010;126;e526-e533. doi: https://doi.org/10.1542/peds.2010-0433.Savino F., Cordisco L., Tarasco V., Calabrese R., Palumeri E., Matteuzzi D. Molecular identification of coliformbacteria fromcolicky breastfed infants. Acta Paediatr. 2009;98:1582-8. doi: 10.1111/j.1651-2227.2009.01419.x.Savino F., Cordisco L., Tarasco V., Calabrese R., Palumeri E., Matteuzzi D. Molecular identification of coliformbacteria fromcolicky breastfed infants. Acta Paediatr. 2009;98:1582-8. doi: 10.1111/j.1651-2227.2009.01419.x.Rhoads J.M., Fatheree N.Y., Norori J., Liu Y., Lucke J.F., Tyson J.E. et al. Altered fecal microflora and increased fecal calprotectin in infants with colic. J Pediatr. 2009;155:823-8. doi: 10.1016/j.jpeds.2009.05.012.Rhoads J.M., Fatheree N.Y., Norori J., Liu Y., Lucke J.F., Tyson J.E. et al. Altered fecal microflora and increased fecal calprotectin in infants with colic. J Pediatr. 2009;155:823-8. doi: 10.1016/j.jpeds.2009.05.012.Savino F., Cresi F., Pautasso S., Palumeri E., Tullio V., Roana J. et al. Intestinal microflora in breastfed colicky and non-colicky infants. Acta Paediatr. 2004;93:825-9. Available at: https://www.ncbi.nlm.nih.gov/pubmed/15244234.Savino F., Cresi F., Pautasso S., Palumeri E., Tullio V., Roana J. et al. Intestinal microflora in breastfed colicky and non-colicky infants. Acta Paediatr. 2004;93:825-9. Available at: https://www.ncbi.nlm.nih.gov/pubmed/15244234.Sung V., D’Amico F., Cabana M.D., Chau K., Koren G., Savino F., Szajewska H., Deshpande G., Dupont C., Indrio F., Mentula S., Partty A., Tancredi D. Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis. Pediatrics. 2018;141(1). pii: e20171811. doi: 10.1542/peds.2017-1811.Sung V., D’Amico F., Cabana M.D., Chau K., Koren G., Savino F., Szajewska H., Deshpande G., Dupont C., Indrio F., Mentula S., Partty A., Tancredi D. Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis. Pediatrics. 2018;141(1). pii: e20171811. doi: 10.1542/peds.2017-1811.Mai T., Fatheree N.Y., Gleason W., Liu Y., Rhoads J.M. Infantile Colic: New Insights into an Old Problem. Gastroenterology Clinics of North America. 2018;829-844. doi: 10.1016/j.gtc.2018.07.008.Mai T., Fatheree N.Y., Gleason W., Liu Y., Rhoads J.M. Infantile Colic: New Insights into an Old Problem. Gastroenterology Clinics of North America. 2018;829-844. doi: 10.1016/j.gtc.2018.07.008.Savino F., Garro M., Montanari P., Galliano I., Bergallo M. Crying Time and RORγ/FOXP3 Expression in Lactobacillus reuteri DSM17938Treated Infants with Colic: A Randomized Trial. The journal of pediatrics. 2018;192:171-177.e1. doi: 10.1016/j.jpeds.2017.08.062.Savino F., Garro M., Montanari P., Galliano I., Bergallo M. Crying Time and RORγ/FOXP3 Expression in Lactobacillus reuteri DSM17938Treated Infants with Colic: A Randomized Trial. The journal of pediatrics. 2018;192:171-177.e1. doi: 10.1016/j.jpeds.2017.08.062.Sefik E., Geva-Zatorsky N., Oh S., Konnikova L., Zemmour D., Manson McGuire A., et al. Individual intestinal symbionts induce a distinct population of RORg+ regulatory T cells. Science. 2015;6251:993-7.Sefik E., Geva-Zatorsky N., Oh S., Konnikova L., Zemmour D., Manson McGuire A., et al. Individual intestinal symbionts induce a distinct population of RORg+ regulatory T cells. Science. 2015;6251:993-7.Wu R.Y., Pasyk M., Wang B., Forsythe P., Bienenstock J., Mao Y.–K., Sharma P., Stanisz A.M., Kunze W.A. Spatiotemporal maps reveal regional differences in the effects on gut motility for Lactobacillus reuteri and rhamnosus strains. Neurogastroenterology& Motility. 2013;25(3):205-14. doi: 10.1111/nmo.12072.Wu R.Y., Pasyk M., Wang B., Forsythe P., Bienenstock J., Mao Y.–K., Sharma P., Stanisz A.M., Kunze W.A. Spatiotemporal maps reveal regional differences in the effects on gut motility for Lactobacillus reuteri and rhamnosus strains. Neurogastroenterology& Motility. 2013;25(3):205-14. doi: 10.1111/nmo.12072.Morgun A., Dzutsev A., Dong X., Greer R.L., Sexton D.J., Ravel J., Schuster M., Hsiao W., Matzinger P., Shulzhenko N. Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks. Gut. 2015;64(11):1732–1743. doi: 10.1136/gutjnl-2014-308820.Morgun A., Dzutsev A., Dong X., Greer R.L., Sexton D.J., Ravel J., Schuster M., Hsiao W., Matzinger P., Shulzhenko N. Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks. Gut. 2015;64(11):1732–1743. doi: 10.1136/gutjnl-2014-308820.Lionetti E., Castellaneta S., Minielloet V.L., Magista A.M. Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter pylori treatment in children: a randomised placebo controlled trial. Aliment Pharmacol Ther. 2006;24:1461-1468. doi: 10.1111/j.1365-2036.2006.03145.x.Lionetti E., Castellaneta S., Minielloet V.L., Magista A.M. Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter pylori treatment in children: a randomised placebo controlled trial. Aliment Pharmacol Ther. 2006;24:1461-1468. doi: 10.1111/j.1365-2036.2006.03145.x.Cimperman L., Best K., Bayless G., Mordarski B., Smith M. et al. A Randomised, double-blind, placebo-controlled pilot study of Lactobacillus reuteri for the prevention of antibiotic-associated diarrhoea in hospitalise adults. J Clin Gastroenterol. 2011;45(9):785-9. doi: 10.1097/MCG.0b013e3182166a42.Cimperman L., Best K., Bayless G., Mordarski B., Smith M. et al. A Randomised, double-blind, placebo-controlled pilot study of Lactobacillus reuteri for the prevention of antibiotic-associated diarrhoea in hospitalise adults. J Clin Gastroenterol. 2011;45(9):785-9. doi: 10.1097/MCG.0b013e3182166a42.Szajewska H., Guarino A., Hojsak I., Indrio F., Kolacek S., Shamir R., Vandenplas Y., Weizman Z. The use of probiotics for the management of acute gastroenteritis: a position paper by the Espghan Working Group for probiotics. J Pediatr Gastroenterol Nutr. 2014;58:531–539. doi: 10.1097/MPG.0000000000000320.Szajewska H., Guarino A., Hojsak I., Indrio F., Kolacek S., Shamir R., Vandenplas Y., Weizman Z. The use of probiotics for the management of acute gastroenteritis: a position paper by the Espghan Working Group for probiotics. J Pediatr Gastroenterol Nutr. 2014;58:531–539. doi: 10.1097/MPG.0000000000000320.

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