The role of commensal bacteria in the regulation of sensitization to food allergens

Abstract

The prevalence of life-threatening anaphylactic responses to food is rising at an alarming rate. The emerging role of the gut microbiota in regulating food allergen sensitization may help explain this trend. The mechanisms by which commensal bacteria influence sensitization to dietary antigens are only beginning to be explored. We have found that a population of mucosa-associated commensal anaerobes prevents food allergen sensitization by promoting an IL-22-dependent barrier protective immune response that limits the access of food allergens to the systemic circulation. This early response is followed by an adaptive immune response mediated in part by an expansion of Foxp3+ Tregs that fortifies the tolerogenic milieu needed to maintain non-responsiveness to food. Bacterial metabolites, such as short-chain fatty acids, may contribute to the process through their ability to promote Foxp3+ Treg differentiation. This work suggests that environmentally induced alterations of the gut microbiota offset the regulatory signals conferred by protective bacterial species to promote aberrant responses to food. Our research presents exciting new possibilities for preventing and treating food allergies based on interventions that modulate the composition of the gut microbiota.

Allergen Immunization Induces Major Changes in Microbiota Composition and Short-Chain Fatty Acid Production in Different Gut Segments in a Mouse Model of Lupine Food Allergy

“…2b, 4), in agreement with both human and animal studies, supporting an important role of this bacteria class in relation to allergy [15, 21, 22]. Clostridia bacteria are anaerobic spore-forming Firmicutes bacteria, which is a dominant class of commensal bacteria, residing in close proximity to the colonic epithelium [18]. This may explain why the colon was the most sensitive segment in which to detect changes for the Clostridia OTUs (see below).…”

“…Food allergy develops following loss of oral tolerance, which allows allergic sensitization [17]. Since barrier integrity and function is important to maintain oral tolerance to proteins, the known role of the microbiome in maintaining the barrier homeostasis is probably important to reduce allergen uptake and/or allergen interaction with the epithelial and immune cells [6, 18]. Further, metabolites produced by the microbiota can affect immune cell function directly, like for instance the reported effects of short-chain fatty acids (SCFAs) protecting against oral sensitization in mice by numerous pathways in the gastrointestinal tract, including IgA production, CD103+ dendritic cells [19], and regulatory T cell function [20].…”

“…Alongside, the immune cell composition also varies throughout the intestines, and these regional variations in microbiota and immune cells will obviously influence the interactions between the two [32]. It has been suggested that the SCFAs, which are mainly produced by bacteria in the colon, may be absorbed and transferred from the colon to the intestines via blood and lymph circulation, there contributing to immune regulation (sensitization vs. tolerance) [18]. Little is known, however, about how the differences in microbial composition and SCFA production between allergic and control animals are reflected throughout the gastrointestinal tract.…”

Commensal bacteria protect against food allergen sensitization

“…Rising disease prevalence over a short period cannot be explained by genetic variation alone, renewing interest in the role of the environment in shaping allergic sensitization to food (2,3). First proposed more than 20 years ago, the hygiene hypothesis suggested that societal efforts to reduce exposure to infectious microbes early in life have deprived the immune system of immunoregulatory stimulation necessary for protection against allergic disease (4).…”

Targeting IgE to facilitate oral immunotherapy for food allergy: a potential new role for anti-IgE therapy?

“…In the USA, in 2009-2010, 8% of children were estimated to have food allergy, and 39% of these children experienced severe reactions [2]. Moreover, the prevalence of food allergy in the USA, UK and China appears to have doubled or tripled over the past 12 years, likely related to environmental changes, for example, decreased prevalence of certain infections or alterations in the intestinal microbiome [3][4][5]. Furthermore, the increasing prevalence coupled with the absence of effective therapies, other than avoidance of the offending food and prompt treatment of allergic reactions that develop after accidental ingestion, renders food allergy as an urgent clinical problem.…”