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Probiotics are an attractive target for reducing the incidence of allergic disease. Bacillus subtilis is a gut-associated probiotic bacteria that can suppress allergic lung disease; however, it is not clear for how long this protection lasts. We exposed C57Bl/6 mice to B. subtilis via oral gavage and challenged them with intranasal house-dust mite for up to 8 weeks. We found that B. subtilis treatment was able to provide protection from eosinophil infiltration of the airways for 3 weeks. This loss of protection correlated with an increase in the eosinophil chemoattractant CCL24. Additionally, we demonstrate that B. subtilis treatment altered the bacterial composition by increasing the phylum Bacteroidetes and Verrucomicorbiota. The phylum Verrucomicorbiota was reduced in B. subtilis-treated mice at 8 weeks when protection was lost. These results support B. subtilis as a prophylactic for preventing the production of allergic lung disease and highlights that protection can last up to 3 weeks. This work also expands our understanding of how B. subtilis mediates protection and that in addition to modifying the immune system it is also altering the host microbiota.

Abstract House-dust mites (HDM) allergy is the prevailing condition in subjects allergic to inhalants. Clinical studies with HDM extracts—either subcutaneous (SCIT) or sublingual (SLIT) have long been characterized by small sample size, varying allergen doses, and poorly defined endpoints assessing disease severity. In the last decade, well-designed, randomized, controlled studies recruiting thousands of patients have been conducted with newly developed HDM sublingual tablets (SQ®-HDM tablets). This drug is easily dispersible in the oral cavity due to the patented Zydis® technology and its allergen composition is balanced in terms of group I and group II major mite allergen content, reflecting the equal contribution of the two components to HDM sensitization. HDM is the most common allergen associated with asthma. Clinical efficacy of the SQ® HDM SLIT-tablet in HDM allergic asthma has been evaluated in randomized, double-blind, placebo-controlled trials. Both endpoints related to “present” asthma control (inhaled corticosteroid—ICS) as well as endpoints related to “future” asthma control (occurrence of asthma exacerbations) were included in these studies, in agreement with GINA (Global Initiative for Asthma) guidelines. Based on the positive results of these studies, SQ®-HDM SLIT-tablets were approved Europe-wide as registered drug for treating moderate-to-severe allergic rhinitis with or without allergic asthma and not well controlled HDM allergic asthma, associated with allergic rhinitis of any severity. GINA guidelines in 2017 included SLIT-tablet-based immunotherapy as an “add-on” treatment for asthmatic patients sensitized to HDM; indeed, allergen immunotherapy (AIT) is considered to be a complementary treatment option that targets the immunological of allergic diseases, representing the only treatment potentially disease-modifier or, at least, with a long-term efficacy. The availability of a safe, standardized, registered treatment for HDM respiratory allergies is pivotal in the immunotherapy field, pushing it out of a century-long limbo of amatorial interest towards the full dignity deserved by the only casual treatment of respiratory allergies.

Background. Atopic dermatitis (AD) is an early and important step in the propagation of the allergic march, enhancing food and respiratory allergies via epicutaneous sensitisation to allergens. Objectives. To determine the prevalence and patterns of aeroallergen sensitisation, asthma and allergic rhinitis in South African (SA) children with AD. Methods. This was a prospective, observational study in a paediatric university hospital in Cape Town, SA. Children with moderate to severe AD, aged 6 months - 10 years, were recruited randomly and investigated for food sensitisation and allergy. They were assessed for sensitisation to aeroallergens by the immuno solid-phase allergen chip test. House-dust mite DerP and DerF, dust mite Eur m, Timothy grass, Bermuda grass, tree pollen, mould (Alternaria), cat and dog sensitisation patterns were analysed. Symptoms of asthma and allergic rhinitis were elicited using a questionnaire modified from the International Study of Asthma and Allergies in Childhood study questions. Results. One hundred participants (59 black Africans and 41 of mixed ethnicity) were enrolled (median age 42 months). Of the participants, 39% had symptoms of asthma and 53% symptoms of allergic rhinitis; 89% tested positive to at least one aeroallergen, most commonly house-dust mite DerP or DerF (81%), dust mite Eur m (51%), Timothy grass (36%) and cat (35%). Asthma, allergic rhinitis and aeroallergen sensitisation all increased with increasing age, while food allergy decreased with age. Food allergy was not an independent risk factor for respiratory allergies. Children were sensitised to indoor allergens (house-dust mite, pets) from an early age, while pollen allergies increased with age. Conclusions. In this cohort of SA children with moderate to severe AD, comorbidity with respiratory allergies was high. The prevalence of respiratory allergies increased with age while food allergy decreased with age, in keeping with the pattern of the allergic march. Seasonal allergies increased with age, while house-dust mite and pet allergy peaked in younger children, in keeping with early exposure via a defective skin barrier. Early and effective restoration of the skin barrier in AD may be a target for reducing aeroallergen-related diseases.