Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial

Raakel Luoto, Olli Ruuskanen, Matti Waris, Marko Kalliomäki, Seppo Salminen, Erika Isolauri, Raakel Luoto, Olli Ruuskanen, Matti Waris, Marko Kalliomäki, Seppo Salminen, Erika Isolauri

Abstract

Background: Simple and safe strategies for the prevention of viral respiratory tract infections (RTIs) are needed.

Objective: We hypothesized that early prebiotic or probiotic supplementation would reduce the risk of virus-associated RTIs during the first year of life in a cohort of preterm infants.

Methods: In this randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov no. NCT00167700), 94 preterm infants (gestational age, ≥32 + 0 and ≤36 + 6 weeks; birth weight, >1500 g) treated at Turku University Hospital, Turku, Finland, were allocated to receive oral prebiotics (galacto-oligosaccharide and polydextrose mixture, 1:1), a probiotic (Lactobacillus rhamnosus GG, ATCC 53103), or placebo (microcrystalline cellulose) between days 3 and 60 of life. The primary outcome was the incidence of clinically defined virus-associated RTI episodes confirmed from nasal swabs by using nucleic acid testing. Secondary outcomes were the severity and duration of RTIs.

Results: A significantly lower incidence of RTIs was detected in infants receiving prebiotics (rate ratio [RR], 0.24; 95% CI, 0.12-0.49; P < .001) or probiotics (RR, 0.50; 95% CI, 0.28-0.90; P = .022) compared with those receiving placebo. Also, the incidence of rhinovirus-induced episodes, which comprised 80% of all RTI episodes, was found to be significantly lower in the prebiotic (RR, 0.31; 95% CI, 0.14-0.66; P = .003) and probiotic (RR, 0.49; 95% CI, 0.24-1.00; P = .051) groups compared with the placebo group. No differences emerged among the study groups in rhinovirus RNA load during infections, duration of rhinovirus RNA shedding, duration or severity of rhinovirus infections, or occurrence of rhinovirus RNA in asymptomatic infants.

Conclusions: Gut microbiota modification with specific prebiotics and probiotics might offer a novel and cost-effective means to reduce the risk of rhinovirus infections.

Keywords: Galacto-oligosaccharide; Lactobacillus rhamnosus GG; RR; RSV; RTI; Rate ratio; Respiratory syncytial virus; Respiratory tract infection; gut microbiota; polydextrose; prebiotic; preterm infant; probiotic; respiratory tract infections; rhinovirus.

Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Figures

Fig 1
Fig 1
Trial flow of patients.
Fig 2
Fig 2
Median (range) rhinovirus load (log10 copies per sample) obtained when respiratory symptoms were present on days 1, 5, 10, and 15 of the episodes and in asymptomatic infants in the 3 study groups. No significant differences were detected among the study groups at any time point (P = .650 on day 1, P = .605 on day 5, P = .856 on day 10, P = .121 on day 15, and P = .990 in asymptomatic infants). The difference between symptomatic infants on day 1 and asymptomatic infants was significant (P < .001).
Fig 3
Fig 3
Rhinovirus load (log10 copies per sample) obtained in the 5 infants with asymptomatic rhinovirus-positive findings. Rhinovirus quantitative RT-PCR was performed on days 5, 10, and 15 after a verified asymptomatic rhinovirus RNA finding (day 1) to determine the duration of viral shedding.

References

    1. Food and Agriculture Organization of the United Nations, World Health Organization. Report of a joint FAO/WHO expert consultation on evaluation of health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Available at: . Accessed November 2009.
    1. Pineiro M., Asp N.G., Reid G., Macfarlane S., Morelli L., Brunser O. FAO Technical meeting on prebiotics. J Clin Gastroenterol. 2008;42(Suppl 3 Pt 2):S156–S159.
    1. Vouloumanou E.K., Makris G.C., Karageorgopoulos D.E., Falagas M.E. Probiotics for the prevention of respiratory tract infections: a systematic review. Int J Antimicrob Agents. 2009;34:197.
    1. Weichert S., Schroten H., Adam R. The role of prebiotics and probiotics in prevention and treatment of childhood infectious diseases. Pediatr Infect Dis J. 2012;31:859–862.
    1. Sharma A.A., Jen R., Butler A., Lavoie P.M. The developing human preterm neonatal immune system: a case for more research in this area. Clin Immunol. 2012;145:61–68.
    1. Pärtty A., Luoto R., Kalliomäki M., Salminen S., Isolauri E. Effects of early prebiotic and probiotic supplementation on development of gut microbiota and fussing and crying in preterm infants: a randomized, double-blind, placebo-controlled trial. J Pediatr. 2013 Jul 31 [Epub ahead of print]
    1. Peltola V., Waris M., Osterback R., Susi P., Ruuskanen O., Hyypiä T. Rhinovirus transmission within families with children: incidence of symptomatic and asymptomatic infections. J Infect Dis. 2008;197:382–389.
    1. Koskenvuo M., Möttönen M., Waris M., Allander T., Salmi T.T., Ruuskanen O. Human bocavirus in children with acute lymphoblastic leukemia. Eur J Pediatr. 2008;167:1011–1015.
    1. McLeish N.J., Witteveldt J., Clasper L., McIntyre C., McWilliam Leitch EC. Development and assay of RNA transcripts of enterovirus species A to D, rhinovirus species A to C, and human parechovirus: assessment of assay sensitivity and specificity of real-time screening and typing methods. J Clin Microbiol. 2012;50:2910–2917.
    1. Weizman Z., Asli G., Alsheikh A. Effect of a probiotic infant formula on infections in child care centers: comparison of two probiotic agents. Pediatrics. 2005;115:5–9.
    1. Arslanoglu S., Moro G.E., Boehm G. Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life. J Nutr. 2007;137:2420–2424.
    1. Arslanoglu S., Moro G.E., Schmitt J., Tandoi L., Rizzardi S., Boehm G. Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life. J Nutr. 2008;138:1091–1095.
    1. Kukkonen K., Savilahti E., Haahtela T., Juntunen-Backman K., Korpela R., Poussa T. Long-term safety and impact on infection rates of postnatal probiotic and prebiotic (synbiotic) treatment: randomized, double-blind, placebo-controlled trial. Pediatrics. 2008;122:8–12.
    1. Rautava S., Salminen S., Isolauri E. Specific probiotics in reducing the risk of acute infections in infancy−a randomised, double-blind, placebo-controlled study. Br J Nutr. 2009;101:1722–1726.
    1. Taipale T., Pienihäkkinen K., Isolauri E., Larsen C., Brockmann E., Alanen P. Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in infancy. Br J Nutr. 2011;105:409–416.
    1. Maldonado J., Cañabate F., Sempere L., Vela F., Sánchez A.R., Narbona E. Human milk probiotic Lactobacillus fermentum CECT5716 reduces the incidence of gastrointestinal and upper respiratory tract infections in infants. J Pediatr Gastroenterol Nutr. 2012;54:55–61.
    1. Gil-Campos M., López MÁ, Rodriguez-Benítez M.V., Romero J., Roncero I., Linares M.D. Lactobacillus fermentum CECT 5716 is safe and well tolerated in infants of 1-6 months of age: a randomized controlled trial. Pharmacol Res. 2012;65:231–238.
    1. Kalliomäki M., Salminen S., Poussa T., Isolauri E. Probiotics during the first 7 years of life: a cumulative risk reduction of eczema in a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2007;119:1019–1021.
    1. Hooper L.V., Littman D.R., Macpherson A.J. Interactions between the microbiota and the immune system. Science. 2012;336:1268–1273.
    1. Olszak T., An D., Zeissig S., Vera M.P., Richter J., Franke A. Microbial exposure during early life has persistent effects on natural killer T cell function. Science. 2012;336:489–493.
    1. Faith J.J., Guruge J.L., Charbonneau M., Subramanian S., Seedorf H., Goodman A.L. The long-term stability of the human gut microbiota. Science. 2013;341:1237439.
    1. Jartti T., Korppi M. Rhinovirus-induced bronchiolitis and asthma development. Pediatr Allergy Immunol. 2011;22:350–355.
    1. Glück U., Gebbers J.O. Ingested probiotics reduce nasal colonization with pathogenic bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and beta-hemolytic streptococci) Am J Clin Nutr. 2003;77:517–520.
    1. Ichinohe T., Pang I.K., Kumamoto Y., Peaper D.R., Ho J.H., Murray T.S. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc Natl Acad Sci U S A. 2011;108:5354–5359.
    1. Gareau M.G., Sherman P.M., Walker W.A. Probiotics and the gut microbiota in intestinal health and disease. Nat Rev Gastroenterol Hepatol. 2010;7:503–514.
    1. Ganguli K., Meng D., Rautava S., Lu L., Walker W.A., Nanthakumar N. Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation. Am J Physiol Gastrointest Liver Physiol. 2013;304:G132–G141.
    1. Villena J., Chiba E., Tomosada Salva S., Marranzino G., Kitazawa H. Orally administered Lactobacillus rhamnosus modulates the respiratory immune response triggered by the viral pathogen-associated molecular pattern poly(I: C) BMC Immunol. 2012;13:53.
    1. Archambaud C., Nahori M.A., Soubigou Bécavin C., Laval L., Lechat P. Impact of lactobacilli on orally acquired listeriosis. Proc Natl Acad Sci U S A. 2012;109:16684–16689.
    1. Brandtzaeg P. The mucosal immune system and its integration with the mammary glands. J Pediatr. 2010;156(suppl):S8–S15.
    1. Jacobs S.E., Lamson D.M., St George K., Walsh T.J. Human rhinoviruses. Clin Microbiol Rev. 2012;26:135–162.
    1. Ruuskanen O., Waris M., Ramilo O. New aspects on human rhinovirus infections. Pediatr Infect Dis J. 2013;32:553–555.
    1. Jansen R.R., Wieringa J., Koekkoek S.M., Visser C.E., Pajkrt D., Molenkamp R. Frequent detection of respiratory viruses without symptoms: toward defining clinically relevant cutoff values. J Clin Microbiol. 2011;49:2631–2636.
    1. Krilov L.R., Weiner L.B., Yogev R., Fergie J., Katz B.Z., Henrickson K.J. The 2009 COID recommendations for RSV prophylaxis: issues of efficacy, cost, and evidence-based medicine. Pediatrics. 2009;124:1682–1684.
    1. Blanken M.O., Rovers M.M., Molenaar J.M., Winkler-Seinstra P.L., Meijer A., Kimpen J.L. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med. 2013;368:1791–1799.
    1. van Piggelen R.O., van Loon A.M., Krediet T.G., Verboon-Maciolek M.A. Human rhinovirus causes severe infection in preterm infants. Pediatr Infect Dis J. 2010;29:364–365.
    1. Miller E.K., Bugna J., Libster R., Shepherd B.E., Scalzo P.M., Acosta P.L. Human rhinoviruses in severe respiratory disease in very low birth weight infants. Pediatrics. 2012;129:e60–e67.
    1. Hao Q., Lu Z., Dong B.R., Huang C.Q., Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev. 2011;9:CD006895.

Source: PubMed

3
Abonneren