Vorobjova Tamara, Tagoma Aili, Peterson Celeste, Talja Ija, Bärenson Anu, Alnek Kristi, Janson Helis, Metsküla Kaja, Kirss Anne, Sepp Epp, Rööp Tiiu, Kõljalg Siiri, Uibo Raivo
Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Department of Pediatrics, University of Tartu, Children's Clinic of Tartu University Hospital, Tartu, Estonia.
Front Immunol. 2025 Jul 2;16:1613002. doi: 10.3389/fimmu.2025.1613002. eCollection 2025.
The mechanisms underlying gestational diabetes mellitus (GDM) and their impact on maternal and child immunity remain unclear. We hypothesize that gut microbiome alterations and increased small intestinal permeability contribute to GDM. Intestinal fatty acid-binding protein (I-FABP) leakage and elevated IgA/IgG against beta-lactoglobulin may indicate mucosal damage and may serve as biomarkers.
This study evaluated I-FABP and IgA/IgG levels against beta-lactoglobulin in mothers with and without GDM (n=100) and in their children (n=87 at time point 1 (TP1), n=79 at time point 2 (TP2). Levels of antibody to (DSM20083, DSM20086) and (DSM20213) were assessed using flow cytometry. I-FABP was measured using the Hycult Biotech ELISA Kit, and IgA/IgG levels to beta-lactoglobulin were measured using in-house ELISA.
I-FABP and IgA/IgG levels did not significantly differ between mothers with and without GDM. However, children at TP1 had significantly higher I-FABP, IgA and IgG levels to beta-lactoglobulin than their mothers (p<0.01). In children, both I-FABP and IgA levels to beta-lactoglobulin declined with age (p<0.05). The children of mothers with GDM had higher IgA levels to beta-lactoglobulin (p=0.004). I-FABP was inversely correlated with IgA to in GDM mothers (p<0.002). Breastfeed children had higher beta-lactoglobulin IgA/IgG levels (p=0.02), but I-FABP levels did not differ regarding the length of breastfeeding.
Higher I-FABP and IgA levels to beta-lactoglobulin in children suggest increased intestinal permeability compared to adults. Only IgA to beta-lactoglobulin was significantly elevated in the children of mothers with GDM.
妊娠期糖尿病（GDM）的潜在机制及其对母婴免疫的影响尚不清楚。我们推测肠道微生物群改变和小肠通透性增加与妊娠期糖尿病有关。肠道脂肪酸结合蛋白（I-FABP）泄漏以及针对β-乳球蛋白的IgA/IgG升高可能表明黏膜损伤，并可作为生物标志物。
本研究评估了患有和未患有妊娠期糖尿病的母亲（n = 100）及其子女（时间点1（TP1）时n = 87，时间点2（TP2）时n = 79）中I-FABP以及针对β-乳球蛋白的IgA/IgG水平。使用流式细胞术评估针对（DSM20083、DSM20086）和（DSM20213）的抗体水平。使用Hycult Biotech ELISA试剂盒测量I-FABP，并使用内部ELISA测量针对β-乳球蛋白的IgA/IgG水平。
患有和未患有妊娠期糖尿病的母亲之间，I-FABP和IgA/IgG水平无显著差异。然而，TP1时儿童针对β-乳球蛋白的I-FABP、IgA和IgG水平显著高于其母亲（p<0.01）。在儿童中，针对β-乳球蛋白的I-FABP和IgA水平均随年龄下降（p<0.05）。患有妊娠期糖尿病母亲的子女针对β-乳球蛋白的IgA水平较高（p = 0.004）。在妊娠期糖尿病母亲中，I-FABP与针对的IgA呈负相关（p<0.002）。母乳喂养的儿童针对β-乳球蛋白的IgA/IgG水平较高（p = 0.02），但I-FABP水平在母乳喂养时长方面无差异。
与成年人相比，儿童中针对β-乳球蛋白的I-FABP和IgA水平较高表明肠道通透性增加。仅患有妊娠期糖尿病母亲的子女中针对β-乳球蛋白的IgA显著升高。
