Zonulin levels may significantly increase in the months leading up to a celiac disease (CeD) diagnosis, and multiple antibiotic courses may also increase levels of gut permeability, thereby increasing the risk for celiac disease autoimmunity (CDA) in children, according to study findings published in Pediatrics.
Intestinal permeability has been linked to many gastrointestinal diseases, including CeD. However, research regarding the temporal relationship between CeD onset and increased intestinal permeability is unclear. Researchers conducted a study to determine if increased intestinal permeability precedes the onset of CDA among children at risk for the condition.
An increase in intestinal permeability was measured using serum zonulin. The researchers defined CDA by a measurement of elevated celiac autoantibodies in 2 or more occurrences.
Data were collected from the Celiac Disease Genomic Environmental Microbiome and Metabolomic (CD-GEMM) study, which was a longitudinal, prospective, birth cohort study that followed participants from birth to 10 years of age.
Blood samples were drawn periodically to test for celiac autoantibodies and human leukocyte antigen (HLA) genotype. Parents tracked the timing of gluten intake for their children in diaries. Zonulin testing was conducted from the time the patient was aged 1 year to the time of CDA diagnosis.
Of the 500 participants in CD-GEMM, 102 were included in the present study (CDA, n=51; control group, n=51). Of the patients with CDA, 63.7% were female, 31.4% were from the United States, and 68.6% were from Italy.
Among the patients in the CDA group, 28 patients had CeD. There were 26 patients with high-risk genetics, 73 with intermediate-risk genetics, and 3 with low-risk genetics.
Patients with CDA had a significant increase in zonulin in 18.3 (range, 6 -78) months before CDA onset compared with the control group (slope differential=β=0.1277; 95% CI, 0.001-0.255).
Participants from Italy had a higher model-adjusted zonulin mean of 30.24 (standard error [SE], 0.89) compared with patients from the United States with a mean of 25.43 (SE, 1.14).
Antibiotic treatment was used as a proxy for measuring infections. While effects for total viral infections were not significant between zonulin and viral infections, there was a significant association between antibiotic courses and months before CDA diagnosis (P =.04). An increase in antibiotic courses was associated with an increase in zonulin (slope increase=β=0.0243 per antibiotic course; 95% CI, 0.0013-0.0473).
“As the rates of CeD and many other autoimmune diseases have been rising for unknown reasons, examining the pre-disease state may identify strategies to reverse this trend,” study authors noted.
Study limitations include a lack of generalizability, not collecting information on antibiotic course duration, and that currently available assays to measure zonulin do not capture all known proteins in this family.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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