Microbial Dysbiosis Tunes the Immune Response Towards Allergic Disease Outcomes

Clinical Reviews in Allergy & Immunology https://doi.org/10.1007/s12016-022-08939-9 Microbial Dysbiosis Tunes the Immune Response Towards Allergic Disease Outcomes Tracy Augustine1 · Manoj Kumar2 · Souhaila Al Khodor2 · Nicholas van Panhuys1 Accepted: 7 April 2022 © The Author(s) 2022 Abstract The hygiene hypothesis has been popularized as an explanation for the rapid increase in allergic disease observed over the past 50 years. Subsequent epidemiological studies have described the protective effects that in utero and early life exposures to an environment high in microbial diversity have in conferring protective benefits against the development of allergic diseases. The rapid advancement in next generation sequencing technology has allowed for analysis of the diverse nature of microbial communities present in the barrier organs and a determination of their role in the induction of allergic disease. Here, we discuss the recent literature describing how colonization of barrier organs during early life by the microbiota influences the development of the adaptive immune system. In parallel, mechanistic studies have delivered insight into the pathogenesis of disease, by demonstrating the comparative effects of protective T regulatory (Treg) cells, with inflammatory T helper 2 (Th2) cells in the development of immune tolerance or induction of an allergic response. More recently, a significant advancement in our understanding into how interactions between the adaptive immune system and microbially derived factors play a cen‑ tral role in the development of allergic disease has emerged. Providing a deeper understanding of the symbiotic relationship between our microbiome and immune system, which explains key observations made by the hygiene hypothesis. By studying how perturbations that drive dysbiosis of the microbiome can cause allergic disease, we stand to benefit by delineating the protective versus pathogenic aspects of human interactions with our microbial companions, allowing us to better harness the use of microbial agents in the design of novel prophylactic and therapeutic strategies. Keywords Adaptive immunity · Microbiome · CD4 + · Hygiene · Allergy · Atopy Introduction Atopic diseases such as asthma, hay fever, atopic dermati‑ tis, and food allergies represent the most common forms of allergy and are typically defined by the presence of specific immunoglobulin E (sIgE) in serum or a positive skin prick test for common environmental allergens. Constituting the most prevalent chronic condition of childhood, significant propor‑ tions of children develop atopic symptoms in their first year of life. One recent multinational study indicated that 14–28% of infants suffer from atopic dermatitis [1] and rates of recur‑ rent, severe wheezing often used as an early diagnostic marker * Nicholas van Panhuys 1 Laboratory of Immunoregulation, Sidra Medicine, PO BOX 26999, Doha, Qatar 2 Microbiome and Host‑Microbes Interactions Laboratory, Sidra Medicine, Doha, Qatar of heightened risk for the development of asthma have been reported at 16% [2], with some western countries reporting rates of food allergy in excess of 10% at 12 months of age [3]. Increases in the prevalence of these conditions have largely been observed in industrialized countries and have been linked to the modern western diet and lifestyle. Although, there is now also growing evidence of increasing rates of dis‑ ease in rapidly developing countries, showing a correlation with rising economic growth and changes in diet and lifestyle [4]. Numerous studies indicate that these types of allergic responses often occur in a progressive manner termed the “atopic march,” initially presenting early in infants as a skin allergy or eczema that is linked to an underlying food allergy [5]. Subsequently, many children go on to become sensitized to indoor allergens, such as dust or pet dander and to develop allergic rhinitis and then asthma later in childhood or in their early teenage years [5]. Sensitization to outdoor aeroallergens such as grass and tree pollens typically occurs during the later phases of the atopic march, at a time where sensitization to 13 Vol.:(0123456789) Clinical Reviews in Allergy & Immunology food allergens may be seen to decrease [6]. The presence of atopy early in life has been shown to significantly increase the risk for development of additional sensitizations, resulting in a progressive form of atopic disease that advances in an addi‑ tive fashion [7]. Children initially presenting with atopic der‑ matitis, the most commonly diagnosed form of atopy within the first 6 months following birth show increased risk for the development of asthma and allergic rhinitis, with the inci‑ dence of subsequent disease being associated to the severity of the initially diagnosed atopic dermatitis [5]. These findings imply that certain individuals are predisposed to the develop‑ ment of atopic disease, and early age of onset may be indica‑ tive of a susceptible phenotype predictive of increased risk for multiple sensitizations [7]. Many risk factors are associated with the onset of atopic disease, including parental history of atopy [8], breast milk vs. formula feeding [9–12], diet [13], air pollution [14], use of antibiotics [15–17], and mode of deliv‑ ery [18–20], having been well characterized through epide‑ miological studies. Whereas data describing the mechanisms linking these environmental factors with the aberrant activa‑ tion of the adaptive immune system that is responsible for the onset of disease have lagged behind. The adaptive immune system plays a pivotal role in the development of defense against potential infectious path‑ ogens [21] and as the primary function of the adaptive Fig. 1  Influences of environ‑ mental and microbial interac‑ tions on adaptive immune responses and allergic disease. A wide array of factors includ‑ ing, genetic, environmental, and dietary inputs can all potentially modulate the gut immunemicrobiome axis and influence the occurrence of allergy. The microbiome in turn modulates the cohort of regulatory cells induced during development and allows for the establishment of a tolerogenic environment, which mediates the suppression of T cells that arise from inflam‑ matory lineages. However, a dysbiosis of the microbiome leads to impairment of this tolerogenic environment lead‑ ing to development of allergic diseases along with greater expansion in cells of the Th2 inflammatory lineage 13 immune system is to protect against invading pathogens, immune responses generally have an inflammatory effect with potential immunopathological consequences that need to be tightly controlled. To identify potential pathogens, the adaptive immune system requires the ability to distinguish between self and non-self-antigens, whilst simultaneously discerning harmless environmental antigens which can be safely ignored [22]. Occasionally, a failure in the system of checks and bala (...truncated)