Gut microbiome and innate immune response patterns in IgE-associated eczema

Clin Exp Allergy. 2015 Sep;45(9):1419-29. doi: 10.1111/cea.12566.


Background: Gut microbiome patterns have been associated with predisposition to eczema potentially through modulation of innate immune signalling.

Objective: We examined gut microbiome development in the first year of life in relation to innate immune responses and onset of IgE-associated eczema over the first 2.5 years in predisposed children due to maternal atopy [, trial ID ACTRN12606000280505].

Methods: Microbial composition and diversity were analysed with barcoded 16S rRNA 454 pyrosequencing in stool samples in pregnancy and at ages 1 week, 1 month and 12 months in infants (n = 10) who developed IgE-associated eczema and infants who remained free of any allergic symptoms at 2.5 years of age (n = 10). Microbiome data at 1 week and 1 month were analysed in relation to previously assessed immune responses to TLR 2 and 4 ligands at 6 months of age.

Results: The relative abundance of Gram-positive Ruminococcaceae was lower at 1 week of age in infants developing IgE-associated eczema, compared with controls (P = 0.0047). At that age, the relative abundance of Ruminococcus was inversely associated with TLR2 induced IL-6 (-0.567, P = 0.042) and TNF-α (-0.597, P = 0.032); there was also an inverse association between the abundance of Proteobacteria (comprising Gram-negative taxa) and TLR4-induced TNF-α (rs = -0.629, P = 0.024). This relationship persisted at 1 month, with inverse associations between the relative abundance of Enterobacteriaceae (within the Proteobacteria phylum) and TLR4-induced TNF-α (rs = -0.697, P = 0.038) and Enterobacteriaceae and IL-6 (rs = -0.709, P = 0.035). Mothers whose infants developed IgE-associated eczema had lower α-diversity of Bacteroidetes (P = 0.04) although this was not seen later in their infants. At 1 year, α-diversity of Actinobacteria was lower in infants with IgE-associated eczema compared with controls (P = 0.002).

Conclusion and clinical relevance: Our findings suggest that reduced relative abundance of potentially immunomodulatory gut bacteria is associated with exaggerated inflammatory cytokine responses to TLR-ligands and subsequent development of IgE-associated eczema.

Keywords: 16SrRNA; TLR-ligands; diversity; eczema; hygiene hypothesis; innate immunity; intestinal colonization; microbiota; molecular microbiology.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / microbiology
  • Disease Susceptibility
  • Female
  • Gram-Positive Bacteria / classification
  • Gram-Positive Bacteria / immunology*
  • Gram-Positive Bacteria / isolation & purification
  • Humans
  • Immunity, Innate*
  • Immunoglobulin E / immunology*
  • Infant
  • Interleukin-6 / immunology
  • Intestines / immunology
  • Intestines / microbiology*
  • Male
  • Maternal Exposure / adverse effects*
  • Pregnancy
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 4 / immunology
  • Tumor Necrosis Factor-alpha / immunology


  • IL6 protein, human
  • Interleukin-6
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Immunoglobulin E