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)
|