Changes in circulating microRNAs and inflammatory proteins in children with celiac disease during the first year on a gluten-free diet.
Abstract
Background
&
Aims
In celiac disease (CD), mucosal recovery can only be assessed through biopsy, as current serological tests do not reliably reflect histological status or residual inflammation after gluten withdrawal. This limitation is particularly relevant in children, in whom invasive procedures are preferably avoided. Novel serum biomarkers may offer non-invasive and objective insights into intestinal damage, functional recovery, or persistent inflammation. This study aimed to characterize longitudinal changes in selected serum biomarkers from diagnosis through the first year on a gluten-free diet (GFD) and to assess their relationship with nutrient intake in pediatric CD.
Methods
41 children with newly diagnosed CD were assessed at diagnosis (t0), 3 (t3) and 12 months (t12) after initiating a GFD in six hospitals of the Basque Country (Spain). Seven patients failed during the study and 34 finished. Serum inflammatory proteins, circulating microRNAs (miRNAs), citrulline and intestinal fatty acid-binding protein (FABP2) were measured. Dietary intake was evaluated using 3-day 24h food records. Time-point differences were tested with Wilcoxon test and correlations between variables with Spearman's correlation.
Results
After 12 months on a GFD, children with CD showed a statistically significant reduction in pro-inflammatory proteins, particularly in Interleukin-18 (IL-18), C-X-C motif chemokine ligand 11 (CXCL11) and matrix metalloproteinase 10 (MMP-10). In parallel, six circulating miRNAs were significantly altered. No significant changes were observed in FABP2 or citrulline levels. Micronutrient intake improved significantly over the study period, especially for vitamin B12, folate, iron, magnesium and iodine. Furthermore, significant associations were identified between some inflammatory proteins, miRNA and proteins and between micronutrient intake and proteins at different time points.
Conclusions
Some serum biomarkers show statistically significant changes during a GFD and may be useful to monitor pediatric CD. In addition, nutritional intervention improves micronutrient intake in newly diagnosed children with CD.