Therapeutic effects elicited by the probiotic Lacticaseibacillus rhamnosus GG in children with atopic dermatitis. The results of the ProPAD trial

Abstract

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of the pediatric population associated with alteration of skin and gut microbiome. Probiotics have been proposed for AD treatment. The ProPAD study aimed to investigate the therapeutic effects of the probiotic Lacticaseibacillus rhamnosus GG (LGG) in children with AD.

Methods: In total, 100 AD patients aged 6-36 months were enrolled in a randomized, double-blind, controlled trial to receive placebo (Group A) or LGG (1 x 10¹⁰ CFU/daily) (Group B) for 12 weeks. The primary outcome was the evaluation of the efficacy of LGG supplementation on AD severity comparing the Scoring Atopic Dermatitis (SCORAD) index at baseline (T0) and at 12-week (T12). A reduction of ≥8.7 points on the SCORAD index was considered as minimum clinically important difference (MCID). The secondary outcomes were the SCORAD index evaluation at 4-week (T16) after the end of LGG treatment, number of days without rescue medications, changes in Infant Dermatitis Quality Of Life questionnaire (IDQOL), gut microbiome structure and function, and skin microbiome structure.

Results: The rate of subjects achieving MCID at T12 and at T16 was higher in Group B (p < .05), and remained higher at T16 (p < .05)The number of days without rescue medications was higher in Group B. IDQOL improved at T12 in the Group B (p < .05). A beneficial modulation of gut and skin microbiome was observed only in Group B patients.

Conclusions: The probiotic LGG could be useful as adjunctive therapy in pediatric AD. The beneficial effects on disease severity and quality of life paralleled with a beneficial modulation of gut and skin microbiome.

Trial registration: ClinicalTrials.gov NCT03863418.

Keywords: butyrate; gut microbiome; infant dermatitis quality of life questionnaire (IDQOL); scoring atopic dermatitis (SCORAD) index; skin microbiome.

FIGURE 1

The design of PROPAD Trial. * At T12. ** At T4 and T8

FIGURE 2

The flow of patients evaluated for the PROPAD Trial

FIGURE 3

The result of the main study outcome: the rate of children with atopic dermatitis achieving the minimum clinically important difference of ≥8.7 units for the SCORAD index. Placebo = Group A; LGG = Group B. Error bars: 95.00% CI. * Group A vs. Group B, p < .05.

FIGURE 4

The SCORAD index pattern during the trial. (Panel A) Change in SCORAD index from baseline (T0) to the end of study period (T16) in the two study groups. Group A = placebo, group B = LGG. Error bars: ±1.00 SE. *Group A vs. Group B, p < .05. Other significant differences: T0 vs. T8 Group A, p < .05; T0 vs. T8 Group B, p < .05; T0 vs. T12, Group B, p < .05; T0 vs. T16 Group A, p < 0.05; T0 vs. T16 Group B, p < .05; T4 vs. T12 Group B, p < .05; T4 vs. T16 Group B, p < .05. (Panel B) The atopic dermatitis severity pattern, evaluated through the SCORAD index, into the two study groups.

FIGURE 5

The modulation of the gut and skin microbiome in the two study groups. (Panel A) Butyrate concentration in fecal samples of subjects enrolled in the two study groups at baseline (T0) and after 12‐week (T12). Placebo = Group A, LGG = Group B. (Panel B) Skin microbiome composition at genus level in children receiving placebo (Group A) and in children receiving LGG (Group B) in the affected and unaffected skin area. ns, not significant difference; *p < .05; **p < .001.