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

Federico II University

Status and phase: Unknown; Phase 2

Conditions: Cow's Milk Allergy

Treatments: Dietary Supplement: Lactobacillus GG

Study type: Interventional

Funder types: Other

Identifiers

NCT02062476

1/14

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 4 to 48 months old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Treatment with Lactobacillus GG

Experimental group

Description:

extensively hydrolyzed casein formula containing LGG

Treatment:

Dietary Supplement: Lactobacillus GG

Children at diagnosis

No Intervention group