Epigenetic Effects Elicited By Lactobacillus GG In Children With Cow's Milk Allergy

EPIGENETIC EFFECTS ELICITED BY LACTOBACILLUS GG IN CHILDREN WITH COW'S MILK ALLERGY: A POSSIBLE EFFECT OF ATOPIC MARCH

Lactobacillus GG (LGG) is able to exert long lasting effects in children with atopic disorders. We have shown that Nutramigen LGG accelerates tolerance acquisition in infants with cow's milk allergy (CMA). The mechanisms of these effects are still largely undefined. The effect of LGG could be related at least in part by the immunoregulatory role played by LGG. This probiotic can balance the generation of cytokines possibly involved in IgE- or non-IgE-mediated CMA (i.e., IL-4, IL-5, IL-10, IFN-γ , TGF-beta, and TNF-alfa), which can contribute to modulation of inflammatory processes. We have demonstrated that children with IgE-mediated CMA produce significantly higher level of IL-4 and IL-13 in response to cow's milk protein, and that tolerance is associated with a marked reduction of IL-13 production and a concomitant increased frequency of IFN-γ releasing cells.

Epigenetics studies the heritable (and potentially reversible) changes of the genome inherited from one cell generation to the next which alter gene expression but do not involve changes in primary DNA sequences, highlighting the complexity of the inter-relationship between genetics and nutrition. There are three distinct, but closely interacting, epigenetic mechanisms (histone acetylation, DNA methylation, and non-coding microRNAs) that are responsible for modifying the expression of critical genes associated with physiologic and pathologic processes. The profile of epigenetic modifications associated with Th lineage commitment, coupled with the sensitivity of the early developmental period, has led to speculation that factors that disrupt these pathways may increase the risk of allergic diseases. Specifically, effects on DNA methylation and endogenous histone deacetylase inhibitors acting on specific pathways (Th1 and T regulatory cell differentiation) may favour Th2-associated allergic differentiation. MicroRNAs are another structural components of an epigenetic mechanism of post-transcriptional regulation of messenger RNA translation. It has been recently identified a specific Th2-associated miRNA (miR-21) that is critical for the regulation of Th cell polarization.

Study Overview

• Status: Unknown
• Conditions: Cow's Milk Allergy
• Intervention / Treatment: Dietary supplement: Lactobacillus GG

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Roberto Berni Canani, MD, PhD; Phone Number: 0817462680

Study Locations

• Italy
  • Naples, Italy, 80131
    • Recruiting
    • University of Naples Federico II
    • Contact: Roberto Berni Canani; Phone Number: 0817462680

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children aged 4 months-4 years with cow's milk allergy

Exclusion Criteria:

• age higher than 4 years,
• concomitant chronic systemic diseases,
• congenital cardiac defects,
• active tuberculosis,
• autoimmune diseases,
• immunodeficiency,
• chronic inflammatory bowel diseases,
• celiac disease,
• cystic fibrosis,
• metabolic diseases,
• malignancy,
• chronic pulmonary diseases,
• malformations of the gastrointestinal tract,
• suspected eosinophilic esophagitis or eosinophilic enterocolitis,
• suspected food-protein-induced enterocolitis syndrome,
• suspected cow's milk protein-induced anaphylaxis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment with Lactobacillus GG; extensively hydrolyzed casein formula containing LGG	Dietary supplement: Lactobacillus GG
No Intervention: Children at diagnosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to 6 months in tolerance acquisition and epigenetic effects in rtwenty children with cow's milk allergy	The investigators will evaluate in children with CMA if the effect of Lactobacillus GG on tolerance acquisition is mediated at least in part by an epigenetic mechanism.	Baseline, at least after 6 months of therapy

Collaborators and Investigators

• Sponsor: Federico II University

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Anticipated): August 1, 2014

Study Registration Dates

• First Submitted: February 6, 2014
• First Submitted That Met QC Criteria: February 12, 2014
• First Posted (Estimate): February 13, 2014

Study Record Updates

• Last Update Posted (Estimate): February 13, 2014
• Last Update Submitted That Met QC Criteria: February 12, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Milk Hypersensitivity
• Other Study ID Numbers: 1/14