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The impact of probiotics and vitamin C on the prevention of upper respiratory tract symptoms in two preschool children cohorts

  • Zuzana Paduchova (Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University) ;
  • Zuzana Nagyova (JuvenaliaA Paediatric Centre) ;
  • Duolao Wang (Department of Clinical Sciences, Liverpool School of Tropical Medicine) ;
  • Jana Muchova (Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University)
  • Received : 2023.07.10
  • Accepted : 2023.11.16
  • Published : 2024.02.01

Abstract

BACKGROUND/OBJECTIVES: The efficacy of Lab4 probiotic and vitamin C combination on the prevention of upper respiratory tract infections (URTIs) was investigated in two studies with children. Our objective was to pool dataset of 57 preschool children from the PROCHILD study (ISRCTN28722693) and the dataset of 50 preschool matched cohort from the PROCHILD-2 study (ISRCTN26587549) to evaluate the impact of probiotic/vitamin C combination on the prevention of upper respiratory tract symptoms and provide a more robust assessment of effect using detailed individual level data. SUBJECTS/METHODS: The children were supplemented daily for 6 months with either the multistrain probiotic (1.25×1010 cfu/tablet consisting of two strains of Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) plus 50 mg vitamin C or a placebo. RESULTS: In the pooled analysis of the individual participant data (per protocol population), significant reductions were observed for the incidence (-25%; 95% confidence interval [CI], 0.66, 0.85; P < 0.0001) and duration (-14.9 days; 95% CI, -24.8, -5.1; P = 0.0030) of typical URTI symptoms in the active group compared with the placebo. The incidence rates of absenteeism from preschool (IR ratio, 0.75; 95% CI, 0.66, 0.86; P < 0.0001), paediatric visits (IR ratio, 0.56; 95% CI, 0.47; 0.68; P < 0.0001) and antibiotic usage (IR ratio, 0.53; 95% CI, 0.39, 0.71; P < 0.0001) were also significantly reduced. CONCLUSION: The pooled analysis findings of comparable preschool cohorts from two studies indicate that the supplementation with probiotic and vitamin C combination is beneficial in the prevention and management of URTI symptoms.

Keywords

Acknowledgement

The authors wish to thank clinical and research teams for their excellent clinical and technical assistance and all children and parents who participated in both studies.

References

  1. Sun Y, Sundell J. Early daycare attendance increase the risk for respiratory infections and asthma of children. J Asthma 2011;48:790-6.
  2. Allan GM, Arroll B. Prevention and treatment of the common cold: making sense of the evidence. CMAJ 2014;186:190-9.
  3. Gergova RT, Petrova G, Gergov S, Minchev P, Mitov I, Strateva T. Microbiological features of upper respiratory tract infections in Bulgarian children for the period 1998-2014. Balkan Med J 2016;33:675-80.
  4. Jesenak M, Minarikova D. Acute upper respiratory tract infections and its management. Prakt Lek 2020;10:63-70.
  5. Schot MJ, Dekker AR, van Werkhoven CH, van der Velden AW, Cals JW, Broekhuizen BD, Hopstaken RM, de Wit NJ, Verheij TJ. Burden of disease in children with respiratory tract infections in primary care: diary-based cohort study. Fam Pract 2019;36:723-9.
  6. Fendrick AM, Monto AS, Nightengale B, Sarnes M. The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med 2003;163:487-94.
  7. Marengo RL, Ciceran A, Del Rio Navarro BE. Upper respiratory tract infections in children and adults: Burden and management. A narrative summary of selected presentations that took place on 11th-12th May 2017, as part of the Encuentro Latinoamericano de Infecciones Respiratorias Recurrentes (ELAIR) educational event in Mexico City, Mexico. EMJ Respir 2017;5:22-8.
  8. Holstiege J, Schink T, Molokhia M, Mazzaglia G, Innocenti F, Oteri A, Bezemer I, Poluzzi E, Puccini A, Ulrichsen SP, et al. Systemic antibiotic prescribing to paediatric outpatients in 5 European countries: a population-based cohort study. BMC Pediatr 2014;14:174.
  9. World Health Organization. Antibiotic resistance [Internet]. Geneva: World Health Organization; 2020 [cited 2023 September 25]. Available from: https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance.
  10. Sencio V, Machado MG, Trottein F. The lung-gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes. Mucosal Immunol 2021;14:296-304.
  11. Cruz CS, Ricci MF, Vieira AT. Gut microbiota modulation as a potential target for the treatment of lung infections. Front Pharmacol 2021;12:724033.
  12. Yang M, Yang Y, He Q, Zhu P, Liu M, Xu J, Zhao M. Intestinal microbiota-a promising target for antiviral therapy? Front Immunol 2021;12:676232.
  13. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, 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;11:506-14.
  14. Zhao Y, Dong BR, Hao Q. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev 2022;8:CD006895.
  15. King S, Tancredi D, Lenoir-Wijnkoop I, Gould K, Vann H, Connors G, Sanders ME, Linder JA, Shane AL, Merenstein D. Does probiotic consumption reduce antibiotic utilization for common acute infections? A systematic review and meta-analysis. Eur J Public Health 2019;29:494-9.
  16. Hemila H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2013;2013:CD000980.
  17. Garaiova I, Muchova J, Nagyova Z, Wang D, Li JV, Orszaghova Z, Michael DR, Plummer SF, Durackova Z. Probiotics and vitamin C for the prevention of respiratory tract infections in children attending preschool: a randomised controlled pilot study. Eur J Clin Nutr 2015;69:373-9.
  18. Garaiova I, Paduchova Z, Nagyova Z, Wang D, Michael DR, Plummer SF, Marchesi JR, Durackova Z, Muchova J. Probiotics with vitamin C for the prevention of upper respiratory tract symptoms in children aged 3-10 years: randomised controlled trial. Benef Microbes 2021;12:431-40.
  19. Garaiova I, Paduchova Z, Nagyova Z, Wang D, Michael DR, Plummer SF, Marchesi JR, Durackova Z, Muchova J. Probiotics with low dose vitamin C reduce antibiotic prescriptions in children: a secondary analysis of a multicentre randomised double-blind placebo-controlled trial. J Funct Foods 2023;106:105625. CROSSREF
  20. Marteau P, Guyonnet D, Lafaye de Micheaux P, Gelu S. A randomized, double-blind, controlled study and pooled analysis of two identical trials of fermented milk containing probiotic Bifidobacterium lactis CNCM I-2494 in healthy women reporting minor digestive symptoms. Neurogastroenterol Motil 2013;25:331-e252.
  21. Williams EA, Stimpson J, Wang D, Plummer S, Garaiova I, Barker ME, Corfe BM. Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Aliment Pharmacol Ther 2009;29:97-103.
  22. Plummer SF, Garaiova I, Sarvotham T, Cottrell SL, Le Scouiller S, Weaver MA, Tang J, Dee P, Hunter J. Effects of probiotics on the composition of the intestinal microbiota following antibiotic therapy. Int J Antimicrob Agents 2005;26:69-74.
  23. Madden JA, Plummer SF, Tang J, Garaiova I, Plummer NT, Herbison M, Hunter JO, Shimada T, Cheng L, Shirakawa T. Effect of probiotics on preventing disruption of the intestinal microflora following antibiotic therapy: a double-blind, placebo-controlled pilot study. Int Immunopharmacol 2005;5:1091-7.
  24. Plummer S, Weaver MA, Harris JC, Dee P, Hunter J. Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea. Int Microbiol 2004;7:59-62.
  25. Hepburn NJ, Garaiova I, Williams EA, Michael DR, Plummer S. Probiotic supplement consumption alters cytokine production from peripheral blood mononuclear cells: a preliminary study using healthy individuals. Benef Microbes 2013;4:313-7.
  26. King S, Glanville J, Sanders ME, Fitzgerald A, Varley D. Effectiveness of probiotics on the duration of illness in healthy children and adults who develop common acute respiratory infectious conditions: a systematic review and meta-analysis. Br J Nutr 2014;112:41-54.
  27. Laursen RP, Hojsak I. Probiotics for respiratory tract infections in children attending day care centers-a systematic review. Eur J Pediatr 2018;177:979-94.
  28. Hatakka K, Savilahti E, Ponka A, Meurman JH, Poussa T, Nase L, Saxelin M, Korpela R. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ 2001;322:1327.
  29. Hojsak I, Snovak N, Abdovic S, Szajewska H, Misak Z, Kolacek S. Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: a randomized, double-blind, placebo-controlled trial. Clin Nutr 2010;29:312-6.
  30. Kumpu M, Lehtoranta L, Roivainen M, Ronkko E, Ziegler T, Soderlund-Venermo M, Kautiainen H, Jarvenpaa S, Kekkonen R, Hatakka K, et al. The use of the probiotic Lactobacillus rhamnosus GG and viral findings in the nasopharynx of children attending day care. J Med Virol 2013;85:1632-8.
  31. Merenstein D, Murphy M, Fokar A, Hernandez RK, Park H, Nsouli H, Sanders ME, Davis BA, Niborski V, Tondu F, et al. Use of a fermented dairy probiotic drink containing Lactobacillus casei (DN-114 001) to decrease the rate of illness in kids: the DRINK study. A patient-oriented, double-blind, clusterrandomized, placebo-controlled, clinical trial. Eur J Clin Nutr 2010;64:669-77.
  32. Prodeus A, Niborski V, Schrezenmeir J, Gorelov A, Shcherbina A, Rumyantsev A. Fermented milk consumption and common infections in children attending day-care centers: a randomized trial. J Pediatr Gastroenterol Nutr 2016;63:534-43.
  33. Leyer GJ, Li S, Mubasher ME, Reifer C, Ouwehand AC. Probiotic effects on cold and influenza-like symptom incidence and duration in children. Pediatrics 2009;124:e172-9.
  34. Lau AS, Yanagisawa N, Hor YY, Lew LC, Ong JS, Chuah LO, Lee YY, Choi SB, Rashid F, Wahid N, et al. Bifidobacterium longum BB536 alleviated upper respiratory illnesses and modulated gut microbiota profiles in Malaysian pre-school children. Benef Microbes 2018;9:61-70.
  35. Caceres P, Montes S, Vega N, Cruchet S, Brunser O, Gotteland M. Effects of Lactobacillus rhamnosus HN001on acute respiratory infections and intestinal secretory IgA in children. J Pediatr Infect Dis 2010;5:353-62.
  36. Hojsak I, Mocic Pavic A, Kos T, Dumancic J, Kolacek S. Bifidobacterium animalis subsp. lactis in prevention of common infections in healthy children attending day care centers - randomized, double blind, placebo-controlled study. Clin Nutr 2016;35:587-91.
  37. Lazou Ahren I, Berggren A, Teixeira C, Martinsson Niskanen T, Larsson N. Evaluation of the efficacy of Lactobacillus plantarum HEAL9 and Lactobacillus paracasei 8700:2 on aspects of common cold infections in children attending day care: a randomised, double-blind, placebo-controlled clinical study. Eur J Nutr 2020;59:409-17.
  38. Damholt A, Keller MK, Baranowski K, Brown B, Wichmann A, Melsaether C, Eskesen D, Westphal V, Arltoft D, Habicht A, et al. Lacticaseibacillus rhamnosus GG DSM 33156 effects on pathogen defence in the upper respiratory tract: a randomised, double-blind, placebo-controlled paediatric trial. Benef Microbes 2022;13:13-23.
  39. Hay AD, Anderson E, Ingle S, Beck C, Hollingworth W. Respiratory tract infections in children in the community: prospective online inception cohort study. Ann Fam Med 2019;17:14-22.
  40. Burvenich R, Dillen H, Trinh NT, Freer J, Wynants L, Heytens S, De Sutter A, Verbakel JY. Antibiotic use in ambulatory care for acutely ill children in high-income countries: a systematic review and meta-analysis. Arch Dis Child 2022;107:1088-94.
  41. Shi HY, Zhu X, Li WL, Mak JW, Wong SH, Zhu ST, Guo SL, Chan FK, Zhang ST, Ng SC. Modulation of gut microbiota protects against viral respiratory tract infections: a systematic review of animal and clinical studies. Eur J Nutr 2021;60:4151-74.
  42. Lehtoranta L, Latvala S, Lehtinen MJ. Role of probiotics in stimulating the immune system in viral respiratory tract infections: a narrative review. Nutrients 2020;12:3163.
  43. Davies T, Plummer S, Jack A, Allen M, Michael D. Lactobacillus and Bifidobacterium promote antibacterial and antiviral immune response in human macrophages. J Prob Health 2018;6:195.
  44. Webberley TS, Masetti G, Baker LM, Dally J, Hughes TR, Marchesi JR, Jack AA, Plummer SF, Ramanathan G, Facey PD, et al. The impact of Lab4 probiotic supplementation in a 90-day study in wistar rats. Front Nutr 2021;8:778289.