Effect of Lactobacillus rhamnosus GG and vitamin D supplementation on the immunologic effectiveness of grass-specific sublingual immunotherapy in children with allergy

Allergy Asthma Proc. 2016 Jul;37(4):324-34. doi: 10.2500/aap.2016.37.3958.


Background: An important issue in sublingual immunotherapy (SLIT) is how to improve efficacy.

Objective: To compare the clinical and immunologic efficacy of SLIT given alone and, to enhance clinical efficacy, given with probiotic or vitamin D supplementation.

Methods: One hundred children, ages 5-12 years, sensitive to grass pollen, with allergic rhinitis participated in a 5-month prospective, randomized, double-blind, placebo-controlled trial. Children received 5-grass SLIT 300 IR tablets with either vitamin D 1000 IU daily supplementation, probiotic, or placebo. The control group included children with allergy who did not qualify for immunotherapy. Primary end points included a symptom-medication score, lung function, and exhaled nitric oxide concentration. The secondary end point was the immunologic efficacy measured by the following: CD4(+)CD25(+)Foxp3(+) (forkhead box P3) cells, Toll-like receptor (TLR) 4, interleukin (IL) 1, IL-6, tumor necrosis factor, IL-10, and transforming growth factor β-1 levels in cell culture supernatants.

Results: Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+) in children who received SLIT in all the groups were observed compared with control group. In the SLIT-probiotic group, between-group analysis showed significantly higher CD4(+)CD25(+)Foxp3(+) induction compared with the SLIT group and higher reduction in the percentage of TLR-positive cell group compared with the SLIT-vitamin D group (Fig. 1). An increase in CD4(+)CD25(+)Foxp3(+) induction, reduction in TLR-positive cells recruitment and an increase in transforming growth factor β-1 production were independently associated with a better clinical effect of SLIT in children.

Conclusions: We demonstrated the clinical and immunologic effect of probiotic and vitamin D supplementation on SLIT. Probiotic supplementation showed better clinical and immunologic response in children with allergic rhinitis.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Allergens / administration & dosage
  • Allergens / immunology*
  • Biomarkers
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Dietary Supplements*
  • Female
  • Humans
  • Lacticaseibacillus rhamnosus*
  • Male
  • Poaceae / adverse effects*
  • Pollen / immunology
  • Probiotics* / administration & dosage
  • Prognosis
  • Respiratory Function Tests
  • Rhinitis, Allergic, Seasonal / diagnosis
  • Rhinitis, Allergic, Seasonal / drug therapy*
  • Rhinitis, Allergic, Seasonal / immunology*
  • Seasons
  • Sublingual Immunotherapy* / adverse effects
  • Sublingual Immunotherapy* / methods
  • Treatment Outcome
  • Vitamin D / administration & dosage*


  • Allergens
  • Biomarkers
  • Vitamin D