Additive Effect between IL-13 Polymorphism and Cesarean Section Delivery/Prenatal Antibiotics Use on Atopic Dermatitis: A Birth Cohort Study (COCOA)

Abstract

BackgroundAlthough cesarean delivery and prenatal exposure to antibiotics are likely to affect the gut microbiome in infancy, their effect on the development of atopic dermatitis (AD) in infancy is unclear. The influence of individual genotypes on these relationships is also unclear. To evaluate with a prospective birth cohort study whether cesarean section, prenatal exposure to antibiotics, and susceptible genotypes act additively to promote the development of AD in infancy.MethodsThe Cohort for Childhood of Asthma and Allergic Diseases (COCOA) was selected from the general Korean population. A pediatric allergist assessed 412 infants for the presence of AD at 1 year of age. Their cord blood DNA was subjected to interleukin (IL)-13 (rs20541) and cluster-of-differentiation (CD)14 (rs2569190) genotype analysis.ResultsThe combination of cesarean delivery and prenatal exposure to antibiotics associated significantly and positively with AD (adjusted odds ratio, 5.70; 95% CI, 1.19–27.3). The association between cesarean delivery and AD was significantly modified by parental history of allergic diseases or risk-associated IL-13 (rs20541) and CD14 (rs2569190) genotypes. There was a trend of interaction between IL-13 (rs20541) and delivery mode with respect to the subsequent risk of AD. (P for interaction = 0.039) Infants who were exposed prenatally to antibiotics and were born by cesarean delivery had a lower total microbiota diversity in stool samples at 6 months of age than the control group. As the number of these risk factors increased, the AD risk rose (trend p<0.05).ConclusionCesarean delivery and prenatal antibiotic exposure may affect the gut microbiota, which may in turn influence the risk of AD in infants. These relationships may be shaped by the genetic predisposition.

The gut microbiome alterations in allergic and inflammatory skin diseases – an update

“…C‐section delivery combined with prenatal antibiotic treatment is associated with significantly higher AD risk development. Lower intestinal bacterial diversity with higher levels of Bacteroides , Clostridium , Enterobacteriaceae and Staphylococcus early in life has been associated with an increased risk for atopic disease . Early innate immunity responses in the gut, including intestinal defensin secretion, are associated with the emergence of sensitization and atopic dermatitis later in childhood …”

Prenatal antibiotics and atopic dermatitis among 18‐month‐old children in the Danish National Birth Cohort

“…2 Perinatal and post-natal exposure to antibiotics has almost consistently been associated with an increased risk of atopic dermatitis in both human and murine models. 22 The aim of this study was therefore to investigate the association between prenatal antibiotic exposure and atopic dermatitis among children at 18 months, taking the timing of exposure in pregnancy, mode of delivery and maternal atopy into account. 10,[18][19][20][21] Four studies found an increased risk of atopic dermatitis among children exposed to prenatal antibiotics, and one study found no association.…”

Environmental Changes, Microbiota, and Allergic Diseases

“…In its original form, this hypothesis claimed that limiting early-life infections impedes the development of the natural immune system and thereby predisposes individuals to allergic disease 29. The modified "microflora hypothesis" proposes that the overlying hygienic Western lifestyle limits not only infections, but also general microbial exposure and it alters the colonization of the human gut, which in turn disrupts the development of immune systems and ultimately leads to allergic diseases 18,30,31. Infancy and early childhood have been identified as important and vulnerable periods in the development of the gut microbiota, which shapes the disposition to allergic diseases.…”