Lactobacillus rhamnosus Used in the Perinatal Period for the Prevention of Atopic Dermatitis in Infants: A Systematic Review and Meta-Analysis of Randomized Trials

Jeffrey Voigt, Meenal Lele, Jeffrey Voigt, Meenal Lele

Abstract

Background: Numerous systematic reviews and meta-analyses have examined the effects of probiotics used perinatally on prevention or treatment of atopic disease in infants and children. However, to date, no review has examined randomized controlled trials of Lactobacillus rhamnosus, specifically, administered both prenatally and postnatally and its effect over a long period of time.

Objective: The objective was to determine if L. rhamnosus either used solely or in conjunction with other probiotics demonstrates a long-term preventive effect on atopic disease in pediatric patients when used perinatally.

Methods: A systematic review was undertaken to identify those studies where L. rhamnosus was used (either solely or in conjunction with other probiotics). The following databases were searched from the year 2000 through December 8, 2021: PubMed, Cochrane Reviews and Cochrane Central Database of Controlled Trials; systematic reviews were hand searched to identify randomized controlled trials (RCTs). Meta-analytic statistical techniques were then employed. Evaluation of the incidence of atopic eczema was also examined longitudinally based on timeframe. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessments were employed to determine the quality of the evidence.

Results: Eleven randomized controlled trials were identified which examined L. rhamnosus in its effect on atopy. Risk of bias was low on the majority of the domains assessed. Meta-analysis of the timeframes ≤ 2 years (RR 0.60, 95% CI 0.47-0.75; p < 0.00001) and 6-7 years (RR 0.62, 95% CI 0.50-0.75; p < 0.00001) demonstrated statistically significant reductions in atopic eczema with use of L. rhamnosus. For the 4 to 5-year (RR 0.74, 95% CI 0.55-1.00; p = 0.05) and 10-11-year (RR 0.68, 95% CI 0.37-1.27; p = 0.23) timeframes there was no statistically significant reduction. GRADE assessment for each timeframe was considered moderate in two, owing to high attrition rates in all of the studies, and low in two due to imprecision.

Conclusion: Based on the meta-analysis and GRADE assessments, the use of L. rhamnosus with or without other probiotics appears to have a positive effect in reducing the incidence of atopic eczema in pediatric patients at least out to 7 years. Attrition rates temper these findings.

Conflict of interest statement

Jeff Voigt is a paid evidence assessment expert for Lil Mixins, a manufacturer of probiotic supplements. Meenal Lele is an executive for Lil Mixins. Jeff Voigt was provided with financial support for the analysis and development of the manuscript.

© 2022. The Author(s).

Figures

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Fig. 1
Forest plot incidence of atopic eczema/dermatitis,

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Forest plot incidence of atopic…

Fig. 2

Forest plot incidence of atopic eczema/dermatitis, 4–5 years out

Fig. 2
Forest plot incidence of atopic eczema/dermatitis, 4–5 years out

Fig. 3

Forest plot incidence of atopic…

Fig. 3

Forest plot incidence of atopic eczema/dermatitis, 6–7 years out

Fig. 3
Forest plot incidence of atopic eczema/dermatitis, 6–7 years out

Fig. 4

Forest plot incidence of atopic…

Fig. 4

Forest plot incidence of atopic eczema/dermatitis, 11 years out

Fig. 4
Forest plot incidence of atopic eczema/dermatitis, 11 years out
Fig. 2
Fig. 2
Forest plot incidence of atopic eczema/dermatitis, 4–5 years out
Fig. 3
Fig. 3
Forest plot incidence of atopic eczema/dermatitis, 6–7 years out
Fig. 4
Fig. 4
Forest plot incidence of atopic eczema/dermatitis, 11 years out

References

    1. Spergel JM, Paller AS. Atopic dermatitis and the atopic march. J Allergy Clin Immunol. 2003;112(6, Supplement):S118–S127. doi: 10.1016/j.jaci.2003.09.033.
    1. Alduraywish SA, Lodge CJ, Campbell B, Allen KJ, Erbas B, Lowe AJ, et al. The march from early life food sensitization to allergic disease: a systematic review and meta-analyses of birth cohort studies. Allergy. 2016;71(1):77–89. doi: 10.1111/all.12784.
    1. Shoda T, et al. Timing of eczema onset and risk of food allergy at 3 years of age: a hospital-based prospective birth cohort study. J Dermatol Sci. 2016;84(2):144–148. doi: 10.1016/j.jdermsci.2016.08.003.
    1. Mohn CH, et al. incidence trends of atopic dermatitis in infancy and early childhood in a nationwide prescription registry study in Norway. JAMA Netw open. 2018;1(7):e184145. doi: 10.1001/jamanetworkopen.2018.4145.
    1. Pothmann A, et al. The microbiome and atopic dermatitis: a review. Am J Clin Dermatol. 2019;20(6):749–761. doi: 10.1007/s40257-019-00467-1.
    1. Lee E, Lee SY, Kang MJ, Kim K, Won S, Kim BJ, et al. Clostridia in the gut and onset of atopic dermatitis via eosinophilic inflammation. Ann Allergy Asthma Immunol. 2016;117(1):91–2.e1. doi: 10.1016/j.anai.2016.04.019.
    1. Marrs T, et al. Gut microbiota development during infancy: Impact of introducing allergenic foods. J Allergy Clin Immunol. 2021;147(2):613–621.e9. doi: 10.1016/j.jaci.2020.09.042.
    1. Mueller NT, Bakacs E, Combellick J, Girgoryan Z, Dominguez-Bello MG. The infant microbiome development: mom matters. Trends Mol Med. 2015;21(2):109–117. doi: 10.1016/j.molmed.2014.12.002.
    1. Walker RW, Clemente JC, Peter I, Loos RJF. The prenatal gut microbiome: Are we colonized with bacteria in utero? Pediat Obes. 2017;12(Suppl 1):3–17. doi: 10.1111/ijpo.12217.
    1. Jenmalm MC, Björkstén B. Cord blood levels of immunoglobulin G subclass antibodies to food and inhalant allergens in relation to maternal atopy and the development of atopic disease during the first 8 years of life. Clin Exp Allergy. 2000;30:34–40. doi: 10.1046/j.1365-2222.2000.00771.x.
    1. Sandberg M, Frykman A, Ernerudh J, et al. Cord blood cytokines and chemokines and development of allergic disease. Pediatr Allergy Immunol. 2009;20:519–527. doi: 10.1111/j.1399-3038.2008.00794.x.
    1. Rautava S, Luoto R, Salminen S, Isolauri E. Microbial contact during pregnancy, intestinal colonization and human disease. Nat Rev Gastroenterol Hepatol. 2012;9:565–576. doi: 10.1038/nrgastro.2012.144.
    1. Jenmalm MC, Duchen K. Timing of allergy-preventive and immunomodulatory dietary interventions - are prenatal, perinatal or postnatal strategies optimal? Clin Exp Allergy. 2013;43:273–278. doi: 10.1111/cea.12003.
    1. Douwes J, Cheng S, Travier N, et al. Farm exposure in utero may protect against asthma, hay fever and eczema. Eur Respir J. 2008;32:603–611. doi: 10.1183/09031936.00033707.
    1. Hill C, Guarner F, Reid G, 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 Gastroentrol Hepatol 2014;11:506–14.
    1. Pérez-Castillo IM, Fernández-Castillo R, Lasserrot-Caudrado A, Gallo-Vellejo JL, Rojas-Carvajal AM, Agullar-Cordero MJ. Reporting of perinatal outcomes in probiotic randomized controlled trials. A systematic review and meta-analysis. Nutrients. 2021;13:256. doi: 10.3390/nu13010256.
    1. Osborn DA, Sinn JKH. Probiotics in infants for prevention of allergic disease and food hypersensitivity. Cochrane Database Syst Rev. 2007 doi: 10.1002/14651858.CD006475.pub2.
    1. Abrahamsson TR, Wu RY, Jenmalm MC. Gut microbiota and allergy: the importance of the pregnancy period. Ped Res. 2015;77(1):214–219. doi: 10.1038/pr.2014.165.
    1. Dang D, Zhou W, Lun ZJ, Mu X, Wang X, Wu H. Meta-analysis of probiotics and/or prebiotics for the prevention of eczema. J Int Med Res. 2013;4(5):1426–1436. doi: 10.1177/0300060513493692.
    1. Doege K, Grakecki D, Zyriax B-C, Detinkina E, zu Eulenburg C, Buhling KJ. Impact of maternal supplementation with probiotics during pregnancy on atopic eczema in childhood—a meta-analysis. Brit Jrl Nut. 2012;107:1–6. doi: 10.1017/S0007114511003400.
    1. Zuccotti G, Meneghlin F, Aceti A, Barone G, Callegari ML, Di Mauro A, et al. Probiotics for prevention of atopic diseases in infants: systematic review and meta-analysis. Allergy. 2015;70:1356–1371. doi: 10.1111/all.12700.
    1. American Gastroenterological Association Consideration for use of probiotics in gastrointestinal diseases: clinical decision support tool. Gastroenterology. 2020;159(2):706. doi: 10.1053/j.gastro.2020.06.004.
    1. Makrgeorgou A, et al. Probiotics for treating eczema. Cochrane Database Syst Rev. 2018;11:11 CD006135. doi: 10.1002/14651858.CD006135.pub3.
    1. Sestito S, et al. The role of prebiotics and probiotics in prevention of allergic diseases in infants. Front Pediatrics. 2020;8:583946. doi: 10.3389/fped.2020.583946.
    1. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71.
    1. Atopic dermatitis (eczema) - Symptoms and causes - Mayo Clinic. Accessed 1 July 2022
    1. Johansson SGO, Bieber T, Dahl R, Friedman PS, Lanier BQ, et al. Revised nomenclature for allergy for global use: report of the nomenclature review committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113:832–836. doi: 10.1016/j.jaci.2003.12.591.
    1. Nottingham Eczema Severity Score (NESS) - The University of Nottingham. Accessed 1 Sep 2022.
    1. EASI score. Eczema area and severity index | DermNet NZ. Accessed 1 Sep 2022.
    1. Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
    1. Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 7: Considering bias and conflicts of interest among the included studies. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane, 2021. . Accessed 9 Jan 2022.
    1. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane, 2021. . Accessed 9 Jan 2022.
    1. GRADE handbook (). Accessed 1 Oct 2022
    1. Kalliomäki M, Salminen S, Arvilommi H, Kero P, Kokinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomized placebo-controlled trial. Lancet. 2001;357:1076–1079. doi: 10.1016/S0140-6736(00)04259-8.
    1. Wickens K, Black PN, Stanley TV, Mitchell E, Fitzharris P, Tannock GW, Purdie G, the Probiotic Study Group A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2008;122:788–794. doi: 10.1016/j.jaci.2008.07.011.
    1. Kukkonnen K, Savilahti E, Haahtela T, Juntenen-Backman K, Korpela R, Poussa T, et al. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2007;119:192–198. doi: 10.1016/j.jaci.2006.09.009.
    1. Huure A, Laitinen K, Rautava S, Korkeamäki M, Isolauri E. Impact of maternal atopy and probiotic supplementation during pregnancy on infant sensitization: a double blind placebo controlled study. Clin Exp Allergy. 2008;38:1342–1348. doi: 10.1111/j.1365-2222.2008.03008.x.
    1. Rautava S, Kalliomäki M, Isolauri E. Probiotics during pregnancy and breast-feeding might confer immunomodularity protection against atopic disease in the infant. J Allergy Clin Immunol. 2002;109:119–121. doi: 10.1067/mai.2002.120273.
    1. Rautava S, Kainonen E, Salminen S, Isolauri E. Maternal probiotic supplementation during pregnancy and breast-feeding reduces the risk of eczema in the infant. J Allergy Clin Immunol. 2012;130:1355–1360. doi: 10.1016/j.jaci.2012.09.003.
    1. Dotterud CK, Storrø O, Johnsen R, Øien T. Probiotics in pregnant women to prevent allergic disease: a randomized, double blind trial. Br J Dermatol. 2010;163:616–623. doi: 10.1111/j.1365-2133.2010.09889.x.
    1. Simpson MR, Dotterud CK, Storrø O, Johnsen R, Øien T. Perinatal probiotic supplementation in the prevention of allergy related disease: 6 year follow up of a randomised controlled trial. BMC Dermatol. 2015;15:13. doi: 10.1186/s12895-015-0030-1.
    1. Wickens K, Barthow C, Mitchell EA, Kang J, van Zyl N, Purdie G, Stanley T, Fitzharris P, Murphy R, Crane J. Effects of Lactobacillus rhamnosus HN001 in early life on the cumulative prevalence of allergic disease to 11 years. Ped Allergy Immunol. 2018;29:808–814. doi: 10.1111/pai.12982.
    1. Kopp MV, Hennemuth I, Heinzmann A, Urbanek R. Randomized, double-blind, placebo-controlled trial of probiotics for primary prevention: no clinical effects of Lactobacillus GG supplementation. Pediatrics. 2008;121(4):e850–e856. doi: 10.1542/peds.2007-1492.
    1. Ou C-Y, Wang L, Jsu T-Y, Chuang H, Liu C-A, Chang J-C, Yu H-R, Yang KD. Prenatal and postnatal probiotics reduces maternal but not childhood allergic diseases: a randomized, double-blind, placebo-controlled trial. Clin Exp Allergy. 2012;42:1386–1396. doi: 10.1111/j.1365-2222.2012.04037.x.
    1. Pelucchi C, Chatenoud L, Turati F, Galeone C, Moja L, Buach J-F, La Vecchia C. Probiotics supplementation during pregnancy or infancy for the prevention of atopic dermatitis. A meta-analysis. Epidemiology. 2012;23:402–414. doi: 10.1097/EDE.0b013e31824d5da2.
    1. Zhang G-Q, Hu H-J, Liu C-Y, Zhang Q, Shakya S, Li Z-Y. Probiotics for prevention of atopy and food hypersensitivity in early childhood. Medicine. 2016;95(8):e2562. doi: 10.1097/MD.0000000000002562.
    1. Kuang L, Jiang Y. Effect of probiotic supplementation in pregnant women: a meta-analysis of randomized controlled trials. Br J Nutr. 2020;123(8):870–880. doi: 10.1017/S0007114519003374.
    1. Tan-Lim CS, Esteban-Ipac NAR, Recto MST, Castor MAR, Casis-Hao R, Nano ALM. Comparative Effectiveness of probiotic strains on the prevention of pediatric atopic dermatitis: a systematic review and network meta-analysis. Ped Allergy Immunol. 2021;32:1255–1270. doi: 10.1111/pai.13514.
    1. Szajewska H, Horvath A. Lactobacillus rhamnosus GG in the primary prevention of eczema in children: a systematic review and meta-analysis. Nutrients. 2018;10:1319. doi: 10.3390/nu10091319.
    1. Kalliomäki M, Salminen S, Arvilommi H, Kero P, Kokinen P, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomized placebo-controlled trial. Lancet. 2003;361:1869–1871. doi: 10.1016/S0140-6736(03)13490-3.
    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(4):1019–1021. doi: 10.1016/j.jaci.2006.12.608.
    1. Kuitunen M, Kukkonen K, Juntunen-Backman K, Korpela R, Poussa T, Turre T, Haahetela T, Savilathi E. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol. 2009;123:335–341. doi: 10.1016/j.jaci.2008.11.019.
    1. Peldan P, Jukkonen AK, Savilahti E, Kuitunen M. Perinatal probiotics decreased eczema up to 10 years of age, but at 5–10 years, allergic rhino-conjunctivitis was increased. Clin Exp Allergy. 2017;47:975–979. doi: 10.1111/cea.12924.
    1. Wickens K, Black P, Stanley TV, Mitchell E, Barthow C, Fitzharris P, Purdie G, Crane J. A protective effect of Lactobacillus rhamnosus HN001 against eczema in the first 2 years of life persists to age 4 years. Clin Exp Allergy. 2012;42:1071–1079. doi: 10.1111/j.1365-2222.2012.03975.x.
    1. Wickens K, Stanley TV, Mitchell EA, BArthow C, Fitzharris P, Purdie G, Siebers R, Black PN, Crane J. Early supplementation with Lactobacillus rhamnosus Hn001 reduces eczema prevalence to 6 years: does it also reduce atopic sensitization? Clin Exp Allergy. 2013;43:1048–1057. doi: 10.1111/cea.12154.

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