Division of Allergy and Immunology, Department of Pediatrics, Fırat University Faculty of Medicine, Elazığ.
Department of Pediatrics, Fırat University Faculty of Medicine, Elazığ.
Turk J Pediatr. 2023;65(5):758-768. doi: 10.24953/turkjped.2023.389.
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. In this study we aimed to explore the association between food allergies and TLR gene polymorphisms in association with gut microbiota.
Toll-like receptors polymorphism frequencies and some bacteria in the gut microbiota in 130 infants aged 1-24 months with egg and/or milk allergy in a prospective cohort were compared with 110 non-food allergic controls. Four candidate polymorphisms (TLR2 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 TLR4 rs4986790 (Asp299Gly) single nucleotide polymorphism (SNP) major/minor allele 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 difference between groups in terms of genotype frequencies (AA, AG, GG). Gut microbiota analysis revealed increased Firmicutes phylum in stool of the patients with food allergy. Except for TLR4 rs4986791 (Thr399lle) allele, the other TLR polymorphisms were not associated with food allergies in children. When the bacteria in the intestinal microbiota and TLR2 and TLR4 gene polymorphisms were compared; we determined a statistically significant increase in Bifidobacterium concentration in the intestinal microbiota in TLR4 rs4986791 CT heterozygous genotype (p=0.004).
This study demonstrated a partial role of TLR4 gene polymorphism and gut microbiota in the development of food allergies. Future work in this area will be required to clarify the roles of different microbial strains that modulate gut microbiota composition and function in conjunction with TLR transcription pathways.
免疫系统和肠道微生物群之间的相互调节是通过几种机制实现的，包括表达在许多细胞类型上的 toll 样受体（TLR）的参与。在这项研究中，我们旨在探索食物过敏与 TLR 基因多态性与肠道微生物群之间的关联。
在一个前瞻性队列中，比较了 130 名 1-24 个月龄的鸡蛋和/或牛奶过敏婴儿与 110 名非食物过敏对照者的 TLR 多态性频率和肠道微生物群中的某些细菌。通过等位基因鉴别聚合酶链反应（PCR）方法对 4 个候选多态性（TLR2 rs1898830/rs5743708 和 TLR4 rs4986790/rs4986791）进行基因分型。通过高通量测序进行肠道微生物群分析。
TLR4 rs4986790（Asp299Gly）单核苷酸多态性（SNP）的主要/次要等位基因频率在食物过敏患者中为 0.788/0.212，在对照组中为 0.719/0.280（p=0.017）。两组在基因型频率（AA、AG、GG）方面存在统计学差异。肠道微生物群分析显示，食物过敏患者粪便中厚壁菌门增多。除 TLR4 rs4986791（Thr399lle）等位基因外，其他 TLR 多态性与儿童食物过敏无关。当比较肠道微生物群中的细菌和 TLR2 和 TLR4 基因多态性时；我们发现 TLR4 rs4986791 CT 杂合基因型的肠道微生物群中双歧杆菌浓度有统计学意义的增加（p=0.004）。
本研究表明 TLR4 基因多态性和肠道微生物群在食物过敏的发展中起部分作用。未来需要在这一领域开展更多工作，以阐明调节肠道微生物群组成和功能的不同微生物菌株与 TLR 转录途径的作用。
