Evaluation of toll-like receptors 2 and 4 polymorphism and intestinal microbiota in children with food allergy

The prevalence of Immunglobulin E (IgE) and non-IgE mediated food allergy has increased dramatically in recent decades affecting nearly 10% of the population in some countries. Acumulating evidence suggests that resident microbial communities play a key role in early host immunologic development and can modify risk for allergic disorders including food allergy and sensitization. In this context, mutual regulation between immune system and gut microbiota is achieved through several mechanisms including the engagement of toll-like receptors (TLRs) which is expressed on numerous cell types. TLRs, specisifically TLR2 and TLR4 play a pivotal role in suppressing the activation of the inflammatory cascade in order to maintain the balance of intestinal homeostasis and in promoting inflammatory responses to specific pathogenic microorganisms. In this study we aimed to explore association between food allergy and TLR gene polymorphisms in association with gut microbiota. Toll-Like Receptors polymorphism frequencies in 130 infants aged 1,5-23 months with egg and/or milk allergy in a prospective cohort were compared 110 non-food allergic controls. Four candidate polymorhpsims (TLR 2 Rs1898830/Rs5743708 and TLR4 Rs4986790/ Rs4986791) were genotyped by allelic discrimination polymerase chain rection (PCR) method. Gut microbiota analysis was achieved by using high-throughput sequencing. The mutant TLR4 Rs4986790 (Asp299Gly) single nucleotide polymorphism (SNP) major/minor allel frequency was 0.788/0.212 in food allergy patients and 0.719/0.280 in controls (p=0.017). There was a statistically significant differece between groups in terms of genotype frequencies (AA, AG, GG). Gut microbiota analysis revealed increased Firmicutes phylum in gaita of the patients with food allergy. Except for mutant Rs4986791 (Thr399lle) allelle, the other TLR polymorphisms were not associated with food allergy in children. In conclusion, this study demonstrated a partial role of TLR4 gene polymorphism and gut microbiota in the development of food allergy. Future work in this area will be required to clarify the roles of different microbial strains that modulates gut microbiota composition and function in conjunction with TLR transcription pathways. Key Words: Food allergy, Toll-like receptor 2, Toll-like receptor 4, genetic polymorphism, gut microbiota