Abstract
BackgroundAccumulating evidence suggests that the gut microbiota shapes developmental processes within the immune system. Early life antibiotic use is one factor which may contribute to immune dysfunction and the recent surge in allergies by virtue of its effects on gut microbiota.Objective and methodsAs a first step towards determining whether a relationship exists between perinatal antibiotic induced changes in the gut microbiota and the later development of a peanut allergy, we exposed newborn mice to either the broad-spectrum antibiotic vancomycin or to a vehicle for 6 weeks and then used a novel murine model of peanut allergy.ResultsEarly-life treatment with vancomycin resulted in a significant shift in the gut microbiota community characterized by a reduction in the abundance of firmicutes and preponderance of inflammatory proteobacteria. Mice with an antibiotic-altered microbiota, showed a localized allergic-like response characterized by ear swelling and scratching following intra-dermal peanut antigen challenge. Likewise, circulating IgE levels were increased in antibiotic-treated mice, but no evidence of a systemic allergic or anaphylactic-like response was observed. Importantly, we utilized the naturally occurring pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), rather than the more commonly used cholera toxin, as an adjuvant together with the peanut antigen.ConclusionOur data suggest that early antibiotic exposure promotes a shift in the gut microbiota community that may in turn, influence how mice later respond to a TNF-α + antigen challenge. However, further studies verifying the capacity of microbiota restoration to protect against allergic responses will be needed to confirm a causal role of antibiotic-induced microbiota variations in promoting allergic disease phenotypes.
Highlights
Accumulating evidence suggests that the gut microbiota shapes developmental processes within the immune system
In a pilot study, we found that 2 μg of tumor necrosis factor-α (TNF-α) acts as an effective adjuvant to elicit an allergic reaction upon subsequent exposure to the peanut protein antigen through an ear punch coated in Crude peanut extract (CPE) or peanut butter oil
Among mice sensitized with TNF-α alone, those previously exposed to vancomycin had significantly higher ear swelling score than those not exposed to vancomycin (p < 0.05, Fig. 2)
Summary
Accumulating evidence suggests that the gut microbiota shapes developmental processes within the immune system. In addition to aiding in digestion, nutrient absorption, vitamin production, and the prevention of colonization by pathogenic bacteria [12, 13], the gut microbiota plays a central role in immunity and is critical for the proper development of tolerance-inducing regulatory T (Treg) cells and immunoglobulin-producing B cells [14,15,16,17,18] In light of these findings, epidemiological studies supporting the microbiota hypothesis have begun to identify links between early life factors that can alter the normal gut microbiota, including antibiotic use, and the promotion of later allergy development [19]. Antibiotic exposure early in life during the critical perinatal microbial colonization period may be of particular importance, as it appears as though there is a ‘critical window’ during this period in which the gut biota has the greatest potential to exert immunomodulatory effects on the host [17]
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