International Inflammation Network (in-FLAME) of the World Universities Network, Umeå, Sweden.
Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
Clin Exp Allergy. 2015 Sep;45(9):1419-29. doi: 10.1111/cea.12566.
Gut microbiome patterns have been associated with predisposition to eczema potentially through modulation of innate immune signalling.
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].
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.
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).
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.
肠道微生物组模式与特应性皮炎的易感性有关，可能通过调节先天免疫信号。
我们研究了生命的第一年中肠道微生物组的发展与固有免疫反应的关系，并在有特应性母亲的儿童中，在 2.5 年内观察到 IgE 相关特应性皮炎的发病情况[www.anzctr.org.au，试验 ID ACTRN12606000280505]。
在婴儿（n=10）怀孕和 1 周、1 个月和 12 个月时，用带条形码的 16S rRNA 454 焦磷酸测序分析粪便样本中的微生物组成和多样性，这些婴儿发展为 IgE 相关特应性皮炎，而在 2.5 岁时没有任何过敏症状的婴儿（n=10）。在 1 周和 1 个月时分析微生物组数据与 6 个月时对 TLR 2 和 4 配体的免疫反应。
与对照组相比，发展为 IgE 相关特应性皮炎的婴儿在 1 周时肠道中革兰氏阳性 Ruminococcaceae 的相对丰度较低（P=0.0047）。在那个年龄，Ruminococcus 的相对丰度与 TLR2 诱导的 IL-6（-0.567，P=0.042）和 TNF-α（-0.597，P=0.032）呈负相关；变形菌门（包括革兰氏阴性分类群）的丰度与 TLR4 诱导的 TNF-α（rs=-0.629，P=0.024）之间也存在负相关。这种关系在 1 个月时仍然存在，肠杆菌科（变形菌门）与 TLR4 诱导的 TNF-α（rs=-0.697，P=0.038）和肠杆菌科与 IL-6（rs=-0.709，P=0.035）之间呈负相关。其婴儿发展为 IgE 相关特应性皮炎的母亲的拟杆菌门的 α-多样性较低（P=0.04），尽管在她们的婴儿中没有看到这种情况。在 1 岁时，与对照组相比，IgE 相关特应性皮炎患儿的放线菌门的 α-多样性较低（P=0.002）。
我们的研究结果表明，潜在的免疫调节肠道细菌的相对丰度降低与 TLR-配体的过度炎症细胞因子反应和随后的 IgE 相关特应性皮炎的发展有关。
