Cross-talk between airway and gut microbiome links to IgE responses to house dust mites in childhood airway allergies

Abstract

A connection between airway and gut microbiota related to allergen exposure in childhood allergies was not well addressed. We aimed to identify the microbiota alterations in the airway and gut related to mite-specific IgE responses in young children with airway allergies. This study enrolled 60 children, including 38 mite-sensitized children (20 rhinitis and 18 asthma), and 22 non-mite-sensitized healthy controls. Microbiome composition analysis of the throat swab and stool samples was performed using bacterial 16S rRNA sequencing. An integrative analysis of the airway and stool microbial profiling associated with IgE reactions in childhood allergic rhinitis and asthma was examined. The Chao1 and Shannon indices in the airway were significantly lower than those in the stool. Additionally, an inverse association of the airway microbial diversity with house dust mite (HDM) sensitization and allergic airway diseases was noted. Fecal IgE levels were positively correlated with the serum Dermatophagoides pteronyssinus-and Dermatophagoides farinae-specific IgE levels. Airway Leptotrichia spp. related to asthma were strongly correlated with fecal Dorea and Ruminococcus spp., which were inversely associated with fecal IgE levels and risk of allergic rhinitis. Moreover, four airway genera, Campylobacter, Selenomonas, Tannerella, and Atopobium, were negatively correlated with both serum mite-specific and fecal IgE levels. Among them, the airway Selenomonas and Atopobium spp. were positively correlated with stool Blautia and Dorea spp. related to asthma and allergic rhinitis, respectively. In conclusion, airway microbial dysbiosis in response to HDM and its cross-talk with the gut microbial community is related to allergic airway diseases in early childhood. Dysbiosis in the gut microbiota is associated with several respiratory infections and lung diseases, including allergy and asthma 1,2. There is accumulating evidence that a cross-talk exists between gut and lung. The upper gastrointestinal microbiota affects the development of the airway microbiota either by aspiration or metabolite production, leading to changes in the airway microenvironment 3. Conversely, the dysbiosis in the lung microbiota is accompanied by that in the gut microbiota via bloodstream 4. In a recent study, airway microbial dysbiosis appears to be strongly associated with sensitization to house dust mites (HDM), potentially contributing to allergic reactions and airway diseases 5. However, its contribution to the gut-lung axis associated with allergies remains unclear. HDM allergy with an elevated immunoglobulin E (IgE) level is strongly implicated in the allergic rhinitis and asthma pathogeneses in children 6. Clinically, the comorbidity between these two conditions is high for perennial aeroallergens 7,8. Furthermore, IgE is also produced locally in the gut and fecal IgE level could serve as a marker

IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming

“…Counterintuitively, all of the statistically significant OM-85-induced differences we observed occurred in PVG rats, although the biological relevance of these changes is uncertain, given the median magnitude of change was roughly half a percent (or less) in terms of relative abundance. Furthermore, other genera were not affected by OM-85 pretreatment: Dorea remained under-represented in T2hi BN rats both pre-and post-OM-85, consistent with other reports of reduced Dorea in stools of children with mite-sensitised rhinitis (68), and young adults with food allergy and sensitisation (69). Our observation that orally administered OM-85 had significant effects on the lung compartment in asthma-susceptible BN rats does suggest that interactions between the gut and lung contribute to disease expression and resolution.…”

Altered gut microbiome compositions are associated with the severity of asthma

“…On the one hand, it has been demonstrated that a modulation of HDM exposure (which elevated immunoglobulin E level) in case of microbial dysbiosis can change the gut microbial community (65). In addition, IgE is also produced locally in the gut; the particular subsets of airway microbiome dysbiosis-associated HDM-specific IgE response can interact with corresponding gut microbiome by changing the IgE levels in the gut through the gut-lung axis (65,66). On the other hand, the gut microbiome affects the levels of serum IgE depending on metabolites.…”

Multiple nutritional and gut microbial factors associated with allergic rhinitis: the Hitachi Health Study

“…The intestinal relative abundance of Escherichia was higher in children with asthma or rhinitis than in controls 52 . The positive association between Escherichia and asthma was replicated in another study 53 . In infants, a high abundance of E. coli was associated with an increased risk of atopic eczema 54 .…”