Clinical Effects of Probiotics Are Associated With Increased Interferon-γ Responses in Very Young Children With Atopic Dermatitis

Prescott SL, Dunstan JA, Hale J, Breckler L, et al. Clin Exp Allergy . 2005;35:1557–1564 PURPOSE OF THE STUDY. The authors recently demonstrated that young children with moderate-to-severe atopic dermatitis (AD) had significant clinical improvement in the severity and extent of their disease with the use of probiotics. The purpose of this study was to assess the effects of probiotics on underlying immune function and relate that to clinical improvement. STUDY POPULATION. Fifty-six Australian children aged 6 to 23 months with moderate-to-severe AD (based on a modified scoring AD [SCORAD] index of ≥25). METHODS. Subjects were randomly assigned to receive probiotics (1 × 10 9 colony-forming units of Lactobacillus fermentum ; n = 26) or placebo ( n = 27) twice daily for 8 weeks. Peripheral blood mononuclear cells were isolated from 53 children at baseline and at 8 and 16 weeks (8 weeks after the supplementation period). Cytokine (interleukin 5 [IL-5], IL-6, IL-10, IL-13, interferon γ [IFN-γ], and tumor necrosis factor α [TNF-α]) responses to allergens (egg ovalbumin, β-lactoglobulin, and house dust mite), vaccines (tetanus toxoid and diphtheria toxoid), intestinal flora (heat-killed L fermentum ), skin flora (heat-killed Staphylococcus aureus ), S aureus enterotoxin B (SEB), and mitogen (phytohemagglutinin) were assessed. RESULTS. The children who received probiotics showed a significant increase in T-helper 1 cytokine IFN-γ responses to SEB and phytohemagglutinin at 8 and 16 weeks compared with baseline. The increase in IFN-γ response to SEB was directly proportional to the decrease in the severity of AD during the study period. After supplementation with probiotics (week 8) children had significantly higher TNF-α responses to heat-killed L fermentum and heat-killed S aureus compared with those in the placebo group. This was not sustained at 16 weeks. IL-13 (a T-helper type 2 cytokine) responses to ovalbumin decreased significantly during the supplementation period, but this was not sustained after its discontinuation. No other effects of probiotics were seen on allergen-specific responses. CONCLUSIONS. Probiotics led to an increase in IFN-γ responses to nonspecific stimuli (SEB and phytohemagglutinin) and an increase in TNF-α responses to skin and intestinal flora. Clinical improvement in AD severity with probiotics was associated with significant increases in the T-helper 1 IFN-γ responses and altered responses to skin and intestinal flora but not consistent effects on allergen-specific responses. REVIEWER COMMENTS. It is interesting to note that this study did not show any consistent effects of probiotics on allergen-specific responses, which suggests more of an impact on innate immune pathways rather than allergen-specific ones. The results of this study show some promise for the use of probiotics in children with AD. However, there are many variables that need to be addressed, such as impact of underlying food allergy, exposure to antibiotics, and environmental factors. Larger studies are needed to further demonstrate clinical efficacy (short-term and long-term), to determine optimal timing and dosing of treatment, to further investigate immunologic mechanisms, and to determine the impact of probiotic treatment on later development of other atopic disorders (eg, asthma) in young children with AD.