Möchten Sie über diese Zeitschrift informiert bleiben? Klicken Sie bitte auf die Buttons, um unsere Alerts zu abonnieren.
Möchten Sie über diese Zeitschrift informiert bleiben? Klicken Sie bitte auf die Buttons, um unsere Alerts zu abonnieren.
Lacticaseibacillus rhamnosus GG DSM 33156 effects on pathogen defence in the upper respiratory tract: a randomised, double-blind, placebo-controlled paediatric trial
in Beneficial MicrobesSearch for other papers by A. Damholt in
Current site
Google Scholar
Search for other papers by M.K. Keller in
Current site
Google Scholar
Search for other papers by K. Baranowski in
Current site
Google Scholar
Search for other papers by B. Brown in
Current site
Google Scholar
Search for other papers by A. Wichmann in
Current site
Google Scholar
Search for other papers by C. Melsaether in
Current site
Google Scholar
Search for other papers by D. Eskesen in
Current site
Google Scholar
Search for other papers by V. Westphal in
Current site
Google Scholar
Search for other papers by D. Arltoft in
Current site
Google Scholar
Search for other papers by A. Habicht in
Current site
Google Scholar
Search for other papers by Q. Gao in
Current site
Google Scholar
Search for other papers by G. Crawford in
Current site
Google Scholar
Acute upper respiratory tract infections (URTIs) are caused by numerous viruses and bacteria. URTIs can be a cause of morbidity and are among the most common reasons for visiting healthcare practitioners and prescribing antibiotics to children in addition to causing absenteeism from school and work. Oral intake of Lacticaseibacillus rhamnosus GG DSM 33156 has shown beneficial health effects in several clinical trials, primarily relating to immune function and gastrointestinal health in children and adults. It has also been suggested that oral intake of L. rhamnosus GG DSM 33156 can reduce the incidence rate and alleviate symptoms of URTIs in children. We here report the results of a randomised, double-blind, placebo-controlled trial of 619 children aged 2-6 years conducted at a single centre in Scotland. The children, who were in day care or primary school, were followed over a 16-week intervention period with 309 randomised in the active group and 310 in the placebo group. The parents or guardians reported a daily healthcare status and any presumed episodes of URTI, which were subsequently confirmed by a general practitioner. The investigational product was well tolerated in the trial. Although a general trend towards a beneficial effect was observed, this trial did not demonstrate that L. rhamnosus GG DSM 33156 significantly reduced the incidence of URTIs, diagnosed by a general practitioner according to prespecified criteria (primary endpoint). Moreover, none of the secondary efficacy endpoints were met. Applying a Ward’s hierarchical clustering, two separate clusters, focussing on four quality of life-related endpoints, were identified. Cluster 1 was associated with more severe URTI characteristics than cluster 2. Cluster 2 was significantly enriched with children who consumed the product, indicating that the symptoms children experience during an URTI are alleviated by the intake of L. rhamnosus GG DSM 33156. The study is registered at ClinicalTrials.gov ID: NCT03636191.
-
Cotton, M., Innes, S., Jaspan, H., Madide, A. and Rabie, H., 2008. Management of upper respiratory tract infections in children. South African Family Practice 50: 6-12. https://doi.org/10.1080/20786204.2008.10873685
-
Dong, H., Rowland, I. and Yaqoob, P., 2012. Comparative effects of six probiotic strains on immune function in vitro. British Journal of Nutrition 108: 459-470. https://doi.org/10.1017/s0007114511005824
-
Doron, S. and Snydman, D.R., 2015. Risk and safety of probiotics. Clinical Infectious Diseases 60, Suppl. 2: S129-134. https://doi.org/10.1093/cid/civ085
-
Haller, O., Kochs, G. and Weber, F., 2006. The interferon response circuit: induction and suppression by pathogenic viruses. Virology 344: 119-130. https://doi.org/10.1016/j.virol.2005.09.024
-
Hao, Q., Dong, B.R. and Wu, T., 2015. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database of Systematic Reviews: Cd006895. https://doi.org/10.1002/14651858.CD006895.pub3
-
Harata, G., He, F., Hiruta, N., Kawase, M., Kubota, A., Hiramatsu, M. and Yausi, H., 2010. Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses. Letters in Applied Microbiology 50: 597-602. https://doi.org/10.1111/j.1472-765X.2010.02844.x
-
Harata, G., He, F., Kawase, M., Hosono, A., Takahashi, K. and Kaminogawa, S., 2009. Differentiated implication of Lactobacillus GG and L. gasseri TMC0356 to immune responses of murine Peyer’s patch. Microbiology and Immunology 53: 475-480. https://doi.org/10.1111/j.1348-0421.2009.00146.x
-
Hatakka, K., Savilahti, E., Pönkä, A., Meurman, J.H., Poussa, T., Nase, L., Saxelin, M. and Korpela, R., 2001. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ 322: 1327. https://doi.org/10.1136/bmj.322.7298.1327
-
Hill, C., Guarner, F., Reid, G., Gibson, G.R., Merenstein, D.J., Pot, B., Morelli, L., Canani, R.B., Flint, H.J., Salminen, S., Calder, P.C. and Sanders, M.E., 2014. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology and Hepatology 11: 506-514. https://doi.org/10.1038/nrgastro.2014.66
-
Hojsak, I., Abdović, S., Szajewska, H., Milosević, M., Krznarić, Z. and Kolacek, S., 2010a. Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract infections. Pediatrics 125: e1171-1177. https://doi.org/10.1542/peds.2009-2568
-
Hojsak, I., Snovak, N., Abdović, S., Szajewska, H., Misak, Z. and Kolacek, S., 2010b. Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: a randomized, double-blind, placebocontrolled trial. Clinical Nutrition 29: 312-316. https://doi.org/10.1016/j.clnu.2009.09.008
-
International Conference on Harmonisation, 2020. ICH Harmonised guideline integrated addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6(R2) ICH Consensus Guideline. 2016. Available at: https://ichgcp.net/
-
Kawase, M., He, F., Kubota, A., Harata, G. and Hiramatsu, M., 2010. Oral administration of lactobacilli from human intestinal tract protects mice against influenza virus infection. Letters in Applied Microbiology 51: 6-10. https://doi.org/10.1111/j.1472-765X.2010.02849.x
-
Lenoir-Wijnkoop, I., Gerlier, L., Bresson, J.L., Le Pen, C. and Berdeaux, G., 2015. Public health and budget impact of probiotics on common respiratory tract infections: a modelling study. PLoS ONE 10: e0122765. https://doi.org/10.1371/journal.pone.0122765
-
Lu, N., Samuels, M.E., Shi, L., Baker, S.L., Glover, S.H. and Sanders, J.M., 2004. Child day care risks of common infectious diseases revisited. Child: Care, Health and Development 30: 361-368. https://doi.org/10.1111/j.1365-2214.2004.00411.x
-
Mosnier, A., 2002. Place de la prescription antibiotique dans la prise en charge de la grippe. VIIème Journée Nationale des GROG. Paris, 21 November 2002. Available at: http://www.grog.org/documents/jour_2002/amm2.pdf
-
Miettinen, M., Matikainen, S., Vuopio-Varkila, J., Pirhonen, J., Varkila, K., Kurimoto, M. and Julkunen, I., 1998. Lactobacilli and streptococci induce interleukin-12 (IL-12), IL-18, and gamma interferon production in human peripheral blood mononuclear cells. Infection and Immunity 66: 6058-6062. https://doi.org/10.1128/iai.66.12.6058-6062.1998
-
Miettinen, M., Pietilä, T.E., Kekkonen, R.A., Kankainen, M., Latvala, S., Pirhonen, J., Österlund, P., Korpela, R. and Julkunen, I., 2012. Nonpathogenic Lactobacillus rhamnosus activates the inflammasome and antiviral responses in human macrophages. Gut Microbes 3: 510-522. https://doi.org/10.4161/gmic.21736
-
Pohjavuori, E., Viljanen, M., Korpela, R., Kuitunen, M., Tiittanen, M., Vaarala, O. and Savilahti, E., 2004. Lactobacillus GG effect in increasing IFN-gamma production in infants with cow’s milk allergy. Journal of Allergy and Clinical Immunology 114: 131-136. https://doi.org/10.1016/j.jaci.2004.03.036
-
Rijkers, G.T., Bengmark, S., Enck, P., Haller, D., Herz, U., Kalliomaki, M., Kudo, S., Lenoir-Wijnkoop, I., Mercenier, A., Myllyluoma, E., Rabot, S., Rafter, J., Szajewska, H., Watzl, B., Wells, J., Wolvers, D. and Antoine, J.M., 2010. Guidance for substantiating the evidence for beneficial effects of probiotics: current status and recommendations for future research. Journal of Nutrition 140: 671s-676s. https://doi.org/10.3945/jn.109.113779
-
Rocha-Ramírez, L.M., Pérez-Solano, R.A., Castañón-Alonso, S.L., Moreno Guerrero, S.S., Ramírez Pacheco, A., García Garibay, M. and Eslava, C., 2017. Probiotic Lactobacillus strains stimulate the inflammatory response and activate human macrophages. Journal of Immunology Research 2017: 4607491. https://doi.org/10.1155/2017/4607491
-
Salminen, M.K., Tynkkynen, S., Rautelin, H., Saxelin, M., Vaara, M., Ruutu, P., Sarna, S., Valtonen, V. and Järvinen, A., 2002. Lactobacillus bacteremia during a rapid increase in probiotic use of Lactobacillus rhamnosus GG in Finland. Clinical Infectious Diseases 35: 1155-1160. https://doi.org/10.1086/342912
-
Segers, M.E. and Lebeer, S., 2014. Towards a better understanding of Lactobacillus rhamnosus GG – host interactions. Microbial Cell Factories 13, Suppl. 1: S7. https://doi.org/10.1186/1475-2859-13-s1-s7
-
Swain, S.L., McKinstry, K.K. and Strutt, T.M., 2012. Expanding roles for CD4+ T cells in immunity to viruses. Nature Reviews Immunology 12: 136-148. https://doi.org/10.1038/nri3152
-
Tregoning, J.S. and Schwarze, J., 2010. Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. Clinical Microbiology Reviews 23: 74-98. https://doi.org/10.1128/cmr.00032-09
-
Ward, C., 2018. Point-of-care C-reactive protein testing to optimise antibiotic use in a primary care urgent care centre setting. BMJ Open Quality 7: e000391. https://doi.org/10.1136/bmjoq-2018-000391
-
World Medical Association, 2013. Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310: 2191-2194. https://doi.org/10.1001/jama.2013.281053
-
Ygberg, S. and Nilsson, A., 2012. The developing immune system – from foetus to toddler. Acta Paediatrica 101: 120-127. https://doi.org/10.1111/j.1651-2227.2011.02494.x
-
Yoon, Y.K., Park, C.S., Kim, J.W., Hwang, K., Lee, S.Y., Kim, T.H., Park, D.Y., Kim, H.J., Kim, D.Y., Lee, H.J., Shin, H.Y., You, Y.K., Park, D.A. and Kim, S.W., 2017. Guidelines for the antibiotic use in adults with acute upper respiratory tract infections. Infection and Chemotherapy 49: 326-352. https://doi.org/10.3947/ic.2017.49.4.326
Supplementary Materials
| Insgesamt | Letzte 365 Tage | In den letzten 30 Tagen | |
|---|---|---|---|
| Aufrufe von Kurzbeschreibungen | 0 | 0 | 0 |
| Gesamttextansichten | 1563 | 533 | 35 |
| PDF-Downloads | 1990 | 738 | 30 |
Lacticaseibacillus rhamnosus GG DSM 33156 effects on pathogen defence in the upper respiratory tract: a randomised, double-blind, placebo-controlled paediatric trial
in Beneficial MicrobesSearch for other papers by A. Damholt in
Current site
Google Scholar
PubMed
Search for other papers by M.K. Keller in
Current site
Google Scholar
PubMed
Search for other papers by K. Baranowski in
Current site
Google Scholar
PubMed
Search for other papers by B. Brown in
Current site
Google Scholar
PubMed
Search for other papers by A. Wichmann in
Current site
Google Scholar
PubMed
Search for other papers by C. Melsaether in
Current site
Google Scholar
PubMed
Search for other papers by D. Eskesen in
Current site
Google Scholar
PubMed
Search for other papers by V. Westphal in
Current site
Google Scholar
PubMed
Search for other papers by D. Arltoft in
Current site
Google Scholar
PubMed
Search for other papers by A. Habicht in
Current site
Google Scholar
PubMed
Search for other papers by Q. Gao in
Current site
Google Scholar
PubMed
Search for other papers by G. Crawford in
Current site
Google Scholar
PubMed
Acute upper respiratory tract infections (URTIs) are caused by numerous viruses and bacteria. URTIs can be a cause of morbidity and are among the most common reasons for visiting healthcare practitioners and prescribing antibiotics to children in addition to causing absenteeism from school and work. Oral intake of Lacticaseibacillus rhamnosus GG DSM 33156 has shown beneficial health effects in several clinical trials, primarily relating to immune function and gastrointestinal health in children and adults. It has also been suggested that oral intake of L. rhamnosus GG DSM 33156 can reduce the incidence rate and alleviate symptoms of URTIs in children. We here report the results of a randomised, double-blind, placebo-controlled trial of 619 children aged 2-6 years conducted at a single centre in Scotland. The children, who were in day care or primary school, were followed over a 16-week intervention period with 309 randomised in the active group and 310 in the placebo group. The parents or guardians reported a daily healthcare status and any presumed episodes of URTI, which were subsequently confirmed by a general practitioner. The investigational product was well tolerated in the trial. Although a general trend towards a beneficial effect was observed, this trial did not demonstrate that L. rhamnosus GG DSM 33156 significantly reduced the incidence of URTIs, diagnosed by a general practitioner according to prespecified criteria (primary endpoint). Moreover, none of the secondary efficacy endpoints were met. Applying a Ward’s hierarchical clustering, two separate clusters, focussing on four quality of life-related endpoints, were identified. Cluster 1 was associated with more severe URTI characteristics than cluster 2. Cluster 2 was significantly enriched with children who consumed the product, indicating that the symptoms children experience during an URTI are alleviated by the intake of L. rhamnosus GG DSM 33156. The study is registered at ClinicalTrials.gov ID: NCT03636191.
| Insgesamt | Letzte 365 Tage | In den letzten 30 Tagen | |
|---|---|---|---|
| Aufrufe von Kurzbeschreibungen | 0 | 0 | 0 |
| Gesamttextansichten | 1563 | 533 | 35 |
| PDF-Downloads | 1990 | 738 | 30 |
