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

作者：West, C. E.^*; Ryden, P.; Lundin, D.; Engstrand, L.; Tulic, M. K.; Prescott, S. L.

来源：Clinical and Experimental Allergy, 2015, 45(9): 1419-1429.

DOI：10.1111/cea.12566

• 16SrRNA
• diversity
• eczema
• hygiene hypothesis
• innate immunity
• intestinal colonization
• microbiota
• molecular microbiology
• TLR-ligands

BackgroundGut microbiome patterns have been associated with predisposition to eczema potentially through modulation of innate immune signalling. @@@ ObjectiveWe 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 2.5years in predisposed children due to maternal atopy [, trial ID ACTRN12606000280505]. @@@ MethodsMicrobial composition and diversity were analysed with barcoded 16S rRNA 454 pyrosequencing in stool samples in pregnancy and at ages 1week, 1month and 12months in infants (n=10) who developed IgE-associated eczema and infants who remained free of any allergic symptoms at 2.5years of age (n=10). Microbiome data at 1week and 1month were analysed in relation to previously assessed immune responses to TLR 2 and 4 ligands at 6months of age. @@@ ResultsThe relative abundance of Gram-positive Ruminococcaceae was lower at 1week 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- (-0.597, P=0.032); there was also an inverse association between the abundance of Proteobacteria (comprising Gram-negative taxa) and TLR4-induced TNF- (rs=-0.629, P=0.024). This relationship persisted at 1month, with inverse associations between the relative abundance of Enterobacteriaceae (within the Proteobacteria phylum) and TLR4-induced TNF- (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 -diversity of Bacteroidetes (P=0.04) although this was not seen later in their infants. At 1year, -diversity of Actinobacteria was lower in infants with IgE-associated eczema compared with controls (P=0.002). @@@ Conclusion and clinical relevanceOur 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.

• 出版日期2015-9