Abstract
Early life exposure to microbes plays an important role in immune system development. Germ-free mice, or mice colonized with a low-diversity microbiota, exhibit high serum IgE levels. An increase in microbial richness, providing it occurs in a critical developmental window early in life, leads to inhibition of this hygiene-induced IgE. However, whether this inhibition is dependent solely on certain microbial species, or is an additive effect of microbial richness, remains to be determined. Here we report that mice colonized with a combination of bacterial species with specific characteristics is required to inhibit IgE levels. These defined characteristics include the presence in early life, acetate production and immunogenicity reflected by induction of IgA. Suppression of IgE did not correlate with production of the short chain fatty acids propionate and butyrate, or induction of peripherally induced Tregs in mucosal tissues. Thus, inhibition of IgE induction can be mediated by specific microbes and their associated metabolic pathways and immunogenic properties.
Highlights
The prevalence of allergies has been increasing over the last 50 years
We have previously shown that mice colonized with the Altered Schaedler Flora (ASF), harboring eight commensal intestinal bacterial species [36], display a dichotomy in terms of development of high IgE levels [11]
Since regulation of IgE is dependent on early-life microbial colonization [11], we investigated whether E. faecalis KB1 and A. muciniphila YL44, the two most dominant members of the Oligo-MM12 consortia in early life (Figure 3F), were able to individually regulate serum IgE levels
Summary
The hygiene hypothesis postulated a link between decreased microbial exposure and increased type 2 immune responses [1]. Later observations revealed that increased hygiene led to changes in both allergic and autoimmune diseases, leading to the counter-regulatory model [2, 3]. Growing understanding of the impact of the intestinal microbiome on immune regulation led to formulation of the microflora hypothesis, which suggested that changes in the composition and richness of gut microbial communities underlies allergic diseases [4]. Elevated total serum IgE levels are a hallmark of allergies but are observed in multiple immunodeficiencies, including some characterized by deficiencies in regulatory T cells [6, 7]. Germ-free mice display abnormally high serum IgE levels [8,9,10,11]
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