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Childhood Exposure to Systemic Antibiotics Linked to Celiac Disease
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Exposure to systemic antibiotics in the first year of life may be a risk factor for later development of celiac disease, according to results of an observational study published in Gastroenterology.
Stine Dydensborg Sander, MD, PhD, of Hans Christian Andersen Children’s Hospital in Denmark, and colleagues wrote that researchers have started looking at the gut microbiota as a potential pathogenesis for autoimmune diseases like celiac disease, particularly early in life.
“The gut microbiota evolves dramatically in the first years of life and stabilizes at 2 to 3 years of age,” they wrote. “The gut microbiota in early life influences the maturation of the immune system and plays a role in the degradation of gluten in the gastrointestinal tract and may thereby affect the immunogenicity of gluten peptides.”
Researchers conducted the study using two nationwide cohorts, one comprising 1,168,656 children born in Denmark between 1995 and 2012, and the other comprising 537,457 children born in Norway between 2004 and 2012. In the Danish cohort, 451,196 children without celiac disease (38.7%) were exposed to antibiotics compared with 622 with celiac disease (43.6%). In the Norwegian cohort, 98,538 children without celiac disease (18.4%) were exposed to antibiotics compared with 390 children with celiac disease (20.3%).
Investigators determined that exposure to systemic antibiotics was associated with diagnosed celiac disease in both cohorts (pooled OR = 1.26; 95% CI, 1.16–1.46), and dose-dependent relationship between an increasing number of antibiotics and celiac disease (pooled OR = 1.08; 95%, 1.05–1.11). The association remained after controlling for hospitalizations for an infectious disease. They found no specific antibiotic or age period with higher risk within the first year.
Sander and colleagues wrote that their findings suggest that antibiotics could be an important component of celiac disease risk, but they should not be regarded as the main factor.
“Future studies should attempt to separate the effect of infections and antibiotics by using more detailed information on indication for use of antibiotics and type of infections preferably by using biomarkers; and to elaborate on types and ages of exposure and interaction between risk factors and if the effect of antibiotic differs between risk groups,” they wrote. – by Alex Young
Disclosures: The authors report no relevant financial disclosures.
Perspective
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Anthony J. DiMarino, Jr., MD
The role of the human microbiome continues to be studied, particularly in gastrointestinal disease. This large study adds further evidence to the importance of microbiome and suggests that a change in its composition could have long-term consequences leading to, or fostering, the development of celiac disease.
The authors suggest if the microbiome is altered within the first year of life, as a result of antibiotic therapy as described by Sander and colleagues, it may alter the microbiome to more closely mimic the characteristics of microbiome in patients with celiac disease. The authors should be congratulated for conducting the largest pediatric study relating the microbiome and celiac disease.
How the microbiome could alter disease is still not known. However, early in life, an abnormal microbiome could delay or alter maturation of the gastrointestinal lymphoid tissue. Also, as noted by the authors and others, degradation of gluten in the gastrointestinal tract may affect immunogenicity of gluten peptides.
Some postulate that the increasing rise of celiac disease over the past 50 years may be due to increased gluten concentration in wheat, or the increased pesticide treatment of growing wheat. Both of these developments may also increase antigenicity and lead to increased development of celiac disease. A concern about the authors’ conclusion is noted by the fact that 30% of the patients could not be fully tracked since the patients’ personal identification numbers were missing.
Further, we do not have full information about the names, or the dosage of the antibiotics taken and the diseases for which they were prescribed. Therefore, we cannot be sure that the children who were taking antibiotics did so for a manifestation of pre-existing celiac disease. Hence, as the authors state, if future studies identify what antibiotics were taken, for how long, and for what disease processes they were being treated and confirm their findings, such a study would support these data. The researchers did try independent methods to address these concerns. For instance, using patients receiving an antifungal cream as a control to identify overly concerned parents was an interesting negative check for selection bias.
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