Zonulin increase may signal celiac diagnosis in children
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Key takeaways:
- Zonulin levels increase as early as 18 months before the onset of celiac disease, a study found.
- Levels also were influenced by antibiotic exposures in the study group.
Zonulin levels rise significantly in children in the months preceding a diagnosis of celiac disease autoimmunity, suggesting it could be used as a biomarker to screen at-risk children for celiac disease, researchers reported in Pediatrics.
For over a decade, researchers at Massachusetts General Hospital have investigated how to predict and prevent autoimmune disease, using celiac disease as a model. A birth cohort study called Celiac Disease, Genomic, Environmental, Microbiome and Metabolomic Study assisted in these investigations.
“In this international study, we follow over 600 infants who are at-risk of celiac disease due to having a family history,” Maureen M. Leonard, MD, MMSc, assistant professor of pediatrics at Harvard Medical School and clinical director of the Mucosal Immunology and Biology Research Center at Mass General, told Healio.
“We collect clinical data and samples from birth through the development of celiac disease or until age 10 in order to be able to study what happens before, during and after the development of autoimmune disease,” Leonard said.
According to Leonard, findings from other studies have suggested that there is increased intestinal permeability in chronic inflammatory and autoimmune diseases like celiac disease, and that increased intestinal permeability — which often comes via zonulin, a protein widely used as a marker of gut permeability — is a key step in the pathogenesis of celiac disease.
“We sought to determine whether we might find increased intestinal permeability even before at-risk children develop the disease,” Leonard said.
Leonard and colleagues selected 51 patients from the cohort who developed celiac disease during the study and 51 control subjects, all ranging in age from 1 to 7 years old.
“We then measured zonulin levels in their blood and examined whether we could identify any changes in zonulin levels in the months and years leading up to celiac disease diagnosis in cases compared to at-risk children that did not develop celiac disease,” Leonard said. “We also examine numerous environmental factors to determine whether they influenced zonulin levels.”
Ultimately, the authors found that children who developed celiac disease autoimmunity (CDA) experienced a significant increase in zonulin in the 18.3 months before CDA compared with those without CDA. Zonulin trajectory was influenced only by increasing the number of antibiotic courses, which increased the slope of trajectory of zonulin over time in patients with CDA.
“We were surprised to find that the trajectory of zonulin level was increasing as early as 18 months before onset of celiac disease,” Leonard said. “This is earlier than we expected. We were also surprised to find that zonulin levels were influenced by the number of antibiotic exposures in cases but not in the control subjects. Since both the cases and controls are at risk of celiac disease this suggests that there may be changes occurring in the years before celiac disease onset.”
The takeaway for primary care providers and pediatricians is that “we are identifying biomarkers that may be helpful in predicting future disease,” Leonard said.
“Here, antibiotic exposure influences zonulin levels over time, and as such, it may influence the risk of developing celiac disease,” Leonard said. “Therefore, physicians should continue to only prescribe antibiotics that are necessary.”
“Our next steps are to understand how antibiotic exposure influences zonulin levels and to validate this in another cohort, if possible,” Leonard said.
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