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

Abstract

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 [www.anzctr.org.au, 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.

• Authors: C E West, P Rydén, D Lundin, L Engstrand, M K Tulic, S L Prescott
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 45 Issue 9 Pg. 1419-29 (Sep 2015) ISSN: 1365-2222 [Electronic] England
• PMID: 25944283 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• 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

Topics

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