Role of Lactobacillus rhamnosus GG in Modulating Immune Responses in Pediatric Food Allergy

Role of Lactobacillus rhamnosus GG in Modulating Immune Responses in Pediatric Food Allergy
Sheyda Hashtroudi,^1,* Monireh Nourabadi,²
1. B.Sc. Student in Microbiology, Faculty of Basic Sciences, Islamic Azad University, Shahre Qods Branch, Tehran, Iran
2. B.Sc. Student in Microbiology, Faculty of Basic Sciences, Islamic Azad University, Shahre Qods Branch, Tehran, Iran
Introduction: Food allergy represents one of the most prevalent non-communicable immunological disorders in children, with a steadily increasing global incidence, substantial economic burden, and significant reduction in quality of life. Current therapeutic approaches, such as allergen avoidance, pharmacological interventions, and allergen-specific immunotherapy (FA-AIT) including oral (OIT), sublingual (SLIT), and epicutaneous (EPIT) methods, offer only partial and inconsistent efficacy, often limited by long-term safety concerns. Emerging evidence highlights the gut microbiome, particularly dysbiotic alterations, as a central factor in the pathogenesis of food allergy. The depletion of beneficial commensals such as Bifidobacterium and Lactobacillus has driven intensive investigation into the immunomodulatory role of probiotics. Among these, Lactobacillus rhamnosus GG (LGG) has shown the most consistent benefits. Clinical trials and meta-analyses suggest that LGG promotes immune tolerance by expanding regulatory T cells (Tregs), shifting cytokine balance (↓IL-4, ↓IL-5, ↑IL-10, ↑TGF-β), reducing allergen-specific IgE, and enhancing IgG4 responses. Adjunctive use of LGG with OIT in peanut allergy has demonstrated significantly higher rates of sustained unresponsiveness and improved immunological profiles. Furthermore, long-term administration of LGG has been associated with reductions in atopic dermatitis severity and improvements in patient-reported outcomes. Despite these promising results, heterogeneity in study designs, strain selection, dosing regimens, and lack of standardized protocols remain major barriers to generalizability. Overall, probiotics (particularly LGG) hold strong potential as adjuvants in pediatric food allergy immunotherapy, but definitive validation requires well-designed, large-scale randomized controlled trials and mechanistic investigations.
Methods: A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, Web of Science, and Medline for publications between 2011 and 2025. Eligible studies included systematic reviews, meta-analyses, and randomized controlled trials (RCTs) investigating probiotics in pediatric food allergy. PRISMA guidelines were applied in several systematic reviews to ensure methodological rigor. Data were extracted on probiotic strains, dosing regimens, duration of intervention, and immunological as well as clinical outcomes.
Results: Mechanistic Evidence: Probiotics enhanced immune tolerance through multiple pathways, including expansion of regulatory T cells (Tregs), reduction of allergen-specific IgE, elevation of IgG4, and cytokine modulation (↓IL-4, ↓IL-5, ↑IL-10, ↑TGF-β). Clinical Trials: Adjunctive administration of Lactobacillus rhamnosus GG (LGG) with oral immunotherapy (OIT) in peanut allergy significantly increased rates of sustained tolerance and reduced allergen-specific IgE . CMA Management: Hydrolyzed casein formulas supplemented with LGG induced tolerance to cow’s milk protein and improved gastrointestinal symptoms in infants . Meta-Analyses : A systematic review (13 studies, 1,608 children) reported inconsistent effects on eczema severity, but long-term administration (≥2 years) of LGG showed the greatest benefit in tolerance induction . A network meta-analysis (16 RCTs, 1,502 children) identified LGG as the most effective probiotic for reducing SCORAD and improving quality of life, whereas L. acidophilus demonstrated the strongest impact on IgE modulation . Conflicting Evidence: Despite promising findings, heterogeneity in strain selection, dosage, and treatment duration limited the ability to establish definitive conclusions .
Conclusion: The current evidence suggests that probiotics, particularly Lactobacillus rhamnosus GG, hold substantial promise as adjuvants in pediatric food allergy immunotherapy. Their benefits include modulation of immune responses, enhancement of sustained tolerance, and improvement of clinical outcomes. However, heterogeneity in study designs, strain variability, and lack of standardized protocols prevent definitive clinical recommendations. Future research should prioritize large-scale, well-designed, long-term randomized controlled trials to establish optimal strains, dosing regimens, and treatment duration, ultimately paving the way toward personalized microbiota-based therapeutic strategies .
Keywords: Food Allergy; Gut Microbiome;Probiotics; Immunotherapy; Lactobacillus rhamnosus GG