The effectiveness of BIFIFORM KIDS in the prevention of the incidence of acute respiratory infections in children

Abstract

Probiotics are widely used as a means of dietary correction of the intestinal microbiota in patients not only with alimentary, but also with allergic and inflammatory diseases. They have systemic effects on the human organism. However, the diversity of the composition of probiotic complexes complicates the determination of the beneficial effects of specific microorganisms on the human body. These circumstances call for more research. Investigation of the effect of probiotic intake on the levels of various cytokines may explain the mechanisms of the beneficial effect of probiotic intake on the functioning of the immune system.

Objective – to study the effectiveness of the probiotic Bifiform Kids for the prevention of respiratory infections in children with recurrent respiratory infections with gastrointestinal allergy symptoms.

Material and methods. The prospective randomized controlled trial included 92 children aged from 4 to 5 years who suffers from more than 5 episodes of respiratory infections per year with gastrointestinal allergy symptoms. Patients from the main group (n=46) were prescribed 2 chewable tablets Bifiform Kids (Lactobacillus rhamnosus GG not less than 1×109 CFU, Bifidobacterium animalis spp. lactis not less than 1×109 CFU, thiamine mononitrate 0.40 mg, pyridoxine hydrochloride 0.50 mg in each) twice per day within 21 days. Patients from the control group (n=46) were prescribed no probiotics during the study period. The study included the measurement of blood serum levels of immunoglobulins A, M, G (by immunoturbodimetry) and E, as well as the concentration of cytokines IL-17, IL-10 (by enzyme immunoassay). Measurements were performed at the 1st day of the study, at the 21st day of the study, and 6 months after the study initiation. The microbiota composition was determined by sequencing the bacterial 16S rRNA genes in DNA preparations isolated from stool samples collected at the start of the study and after 21 days. The Shannon index was calculated for the species of detected bacteria to determine the diversity of the microbiome. The effectiveness of disease prevention was measured by calculating the prevention index and the efficiency coefficient based on the incidence of respiratory infections in both groups during the observation period (6 months).

Results. In the main group, the volume of the commensal flora decreased 3 weeks after the study initiation: Enterobacter from 18.3±19.3 to 10.5±18.1%; Enterococcus from 8.7±16.1 to 3.1±10.0%; Clostridium from 3.1±8.1 to 0.5±2.2%. There was a statistically significant increase in the proportion of representatives of the genus Bifidobacterium by 2.2 times (from 16.9±26.4 to 36.5±31.5%, p=0.0017) and a decrease in the Shannon index from 1.1±2.1 up to 0.4±1.1 (p<0.05). In the control group, there were no statistically significant changes in the microbiota content. In the main group, after 21 days, the blood IL-10 level increased from 11.3±15.4 to 15.7±13.4 pg/ml, and the IL-17 concentration decreased from 8.9±7.7 to 6.5±7.1 pg/ml (p≤0.05) while maintaining this trend by the 6th month of observation. There were no changes in these indicators in children from the control group. The main group demonstrated a significant (р≤0.05) decrease in the level of IgE from 184±121 to 104±67 and 114±54 kU/l, and a significant increase in IgA from 0.73±0.45 to 1.33±0.65 and 1.21±0.57 g/l after 3 weeks and at the end of the probiotic intake, respectively. The level of IgA in the main group remained higher during the study compared to the control group. The main group demonstrated a 3-fold decrease in the incidence of respiratory infections in comparison with the control group. The efficiency index was 3.21, the therapeutic response was 69%.

Conclusion. The results of the study show the effectiveness of the complex probiotic for the respiratory infections prevention in children with gastrointestinal allergy symptoms.

Keywords:probiotics; respiratory infections; frequently ill children; recurrent respiratory infections; Ig E; IgA; IL-17; IL-10; LGG; BB-12

Funding. This study was carried out with the financial support of GlaxoSmithKline Healthcare JSC.

Conflict of interest. The authors declare no conflict of interest.

Contribution. The concept and design of the study – Shikh E.V., Drozdov V.N.; data collection – Shikh E.V., Drozdov V.N., Ermolaeva A.S., Tsvetkov D.N., Bagdasaryan A.A.; statistical data processing – Drozdov V.N., Zhukova O.V.; writing the text – Drozdov V.N., Vorobieva O.A.; editing, approval of the final version of the article, responsibility for the integrity of all parts of the article – all authors.

For citation: Shikh E.V., Drozdov V.N., Vorobieva O.A., Zhukova O.V., Ermolaeva A.S., Tsvetkov D.N., Bagdasaryan A.A. The effectiveness of BIFIFORM KIDS in the prevention of the incidence of acute respiratory infections in children. Voprosy pitaniia [Problems of Nutrition]. 2022; 91 (4): 97–106. DOI: https://doi.org/10.33029/0042-8833-2022-91-4-97-106 (in Russian)

References

1. Frank D.N., Pace N.R. Gastrointestinal microbiology enters the metagenomics era. Curr Opin Gastroenterol. 2008; 24 (1): 4–10. DOI: https://doi.org/10.1097/MOG.0b013e3282f2b0e8

2. Marrs T., Jo J.H., Perkin M.R., Rivett D.W., Witney A.A., Bruce K.D., Logan K., et al. Gut microbiota development during infancy: Impact of introducing allergenic foods. J Allergy Clin Immunol. 2021; 147 (2): 613–21.e9. DOI: https://doi.org/10.1016/j.jaci.2020.09.042

3. Wopereis H., Sim K., Shaw A., Warner J.O., Knol J., Kroll J.S. Intestinal microbiota in infants at high risk for allergy: Effects of prebiotics and role in eczema development. J Allergy Clin Immunol. 2018; 141 (4): 1334–42.e5. DOI: https://doi.org/10.1016/j.jaci.2017.05.054

4. Castellazzi A.M., Valsecchi C., Caimmi S., Licari A., Marseglia A., Leoni M.C., et al. Probiotics and food allergy. Ital J Pediatr. 2013; 39 (1): 47. DOI: https://doi.org/10.1186/1824-7288-39-47

5. Zakharova I.N., Berezhnaya I.V., Klimov L.Ya., Kasyanova A.N., Dedikova O.V., Koltsov K.A. Probiotics in the management of respiratory diseases: ways of interaction and therapeutic perspectives. Meditsinskiy sovet [Medical Council]. 2019; (2): 173–82. DOI: https://doi.org/10.21518/2079-701X-2019-2-173-182 (in Russian)

6. Makarova S.G., Namazova-Baranova L.S., Ereshko O.A., Yasakov D.S., Sadchikov P.E. Intestinal Microbiota and allergy. probiotics and prebiotics in prevention and treatment of allergic diseases. Pediatričeskaâ farmakologiâ [Pediatric Pharmacology]. 2019; 16 (1): 7–18. DOI: https://doi.org/10.15690/pf.v16i1.1999 (in Russian)

7. Sheveleva S.A., Kuvaeva I.B., Efimochkina N.R., Markova Yu.M., Prosyannikov M.Yu. Gut microbiome: from the reference of the norm to pathology. Voprosy pitaniia [Problems of Nutrition]. 2020; 89 (4): 35–51. DOI: https://doi.org/10.24411/0042-8833-2020-10040 (in Russian)

8. Mageswary M.U., Ang X.Y., Lee B.K., Chung Y.F., Azhar S.N.A., Hamid I.J.A., et al. Probiotic Bifidobacterium lactis Probio-M8 treated and prevented acute RTI, reduced antibiotic use and hospital stay in hospitalized young children: a randomized, double-blind, placebo-controlled study. Eur J Nutr. 2022; 61 (3): 1679–91. DOI: https://doi.org/10.1007/s00394-021-02689-8

9. Merenstein D., Gonzalez J., Young A.G., Roberts R.F., Sanders M.E., Petterson S. Study to investigate the potential of probiotics in children attending school. Eur J Clin Nutr. 2011; 65: 447–53. DOI: https://doi.org/10.1038/ejcn.2010.290

10. Semenenko T.A. Epidemiological aspects of nonspecific prevention of infectious diseases. Vestnik Rossiiskoi akademii medetsinskikh nauk [Annals of the Russian Academy of Medical Sciences]. 2001; (11): 25–9. (in Russian)

11. Pessi T., Sütas Y., Hurme M., Isolauri E. Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG. Clin Exp Allergy. 2000; 30 (12): 1804–8. DOI: https://doi.org/10.1046/j.1365-2222.2000.00948.x

12. Tang M.L., Ponsonby A.L., Orsini F., Tey D., Robinson M., Su E.L., et al. Administration of a probiotic with peanut oral immunotherapy: A randomized trial. J Allergy Clin Immunol. 2015; 135 (3): 737–44.e8. DOI: https://doi.org/10.1016/j.jaci.2014.11.034

13. Huang C.F., Chie W.C., Wang I.J. Efficacy of Lactobacillus administration in school-age children with asthma: A randomized, placebo-controlled trial. Nutrients. 2018; 10 (11): 1678. DOI: https://doi.org/10.3390/nu10111678

14. Eslami M., Bahar A., Keikha M., Karbalaei M., Kobyliak N.M., Yousefi B. Probiotics function and modulation of the immune system in allergic diseases. Allergol Immunopathol (Madr). 2020; 48 (6): 771–88. DOI: https://doi.org/10.1016/j.aller.2020.04.005

15. Rumel N.B., Golovacheva E.G., Osidak L.V., Koroleva E.G., Drinev- sky V.P., Muradian A.Ya., et al. The role of specific humoral antibody response in children with acute respiratory infections of various etiology. Meditsinskaya Immunologiya [Medical Immunology (Russia)]. 2003; (5–6): 609–14. (in Russian)

16. Viljanen M., Kuitunen M., Haahtela T., Juntunen-Backman K., Korpela R., Savilahti E. Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants. Pediatr Allergy Immunol. 2005; 16 (1): 65–71. DOI: https://doi.org/10.1111/j.1399-3038.2005.00224.x

17. Lai H.H., Chiu C.H., Kong M.S., Chang C.J., Chen C.C. Probiotic Lactobacillus casei: Effective for managing childhood diarrhea by altering gut microbiota and attenuating fecal inflammatory markers. Nutrients. 2019; 11 (5): 1150. DOI: https://doi.org/10.3390/nu11051150

18. 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 meta-analysis of randomized controlled trials. Adv Nutr. 2020; 11 (4): 979–88. DOI: https://doi.org/10.1093/advances/nmaa003

19. 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. DOI: https://doi.org/10.1097/MD.0000000000004509

20. Laursen R.P., Hojsak I. Probiotics for respiratory tract infections in children attending day care centers-a systematic review. Eur J Pediatr. 2018; 177 (7): 979–94. DOI: https://doi.org/10.1007/s00431-018-3167-1

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

SCImago Journal & Country Rank
Scopus CiteScore
CHIEF EDITOR
CHIEF EDITOR
Viktor A. Tutelyan
Full Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Scientific Director of the Federal Research Centre of Nutrition, Biotechnology and Food Safety (Moscow, Russia)

Journals of «GEOTAR-Media»