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Incidence rates of inflammatory bowel disease (IBD) are increasing worldwide. This correlates with increased consumption of red meats, alcohol, refined sugars, oils and animal fats, typical of a “Western” diet. Poor dietary habits are the most ubiquitous environmental factor implicated in IBD, along with gastrointestinal dysbiosis. Taste genetics and oral receptor expression levels determine dietary preferences and therefore, nutritional intake. Taste receptors (TRs) are also expressed throughout the gastrointestinal tract, where they are involved in modulating metabolic processes and gastrointestinal function. Importantly, these receptors are known to be involved in the modulation of inflammatory processes in the respiratory tract. In this system, TRs detect and respond to bacteria and bacterial signalling molecules and initiate protective responses. We propose that TRs play a similar role in the gastrointestinal tract, thereby modulating risk for IBD. TRs may indirectly affect risk for IBD by altering dietary intake, and therefore microbial composition and function. Alternatively, TRs may directly detect and respond to gastrointestinal bacterial components. Overall, there is evidence to suggest an emerging role for TRs in the aetiology of IBD. Furthermore, targeting these receptors via dietary modulation may have therapeutic potential. Keywords: Taste receptors, Nutrition, Microbiome, Inflammatory bowel disease, Diet

© 2016 American Academy of Allergy, Asthma & Immunology Background Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease. Objective We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches. Methods Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. Results Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21–specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. Conclusion We identify a previously unrecognized role for an miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma.

The synthesis of 3-, 5- and 8-arm dimethylaminoethyl methacrylate star polymers are reported, final Mn (PDI) = 12.2 K (1.09), 18.9K (1.10) and 38.4 K (1.11), respectively. The synthesis of 3-arm methyl methacrylate and dimethylaminoethyl methacrylate block co-polymer stars is also described. Living polymerisation occurred in all cases providing well defined stars with predictable molecular weights and narrow polydispersity. A fluorescent tag, 2-(8-methacryloyloy-3,6-dioxaoctyl)thioxantheno[2,1,9-dej]isoquinoline-1,3-dione, derived from a commercially available pigment, was incorporated into the star polymers. The fluorescence spectra of the polymers prepared were recorded over a range of pH and the peak emission frequency and intensity have been reported, λex = 462 nm. All of the multi-arm polymers exhibit fluorescence across a broad pH range with maximum emission at pH 4. A 3-arm star polymer has been demonstrated to show good bioadhesion in rat tissue. A reduced adhesion in epithelial tissues not covered by a viscoelastic mucus gel indicates an increased tendency for mucoadhesion over bioadhesion. We thank Clariant for the kind donation of the hostasol precursor and Genzyme for part funding this work. D.M. Haddleton would also like to thank Professor John Ebdon for all of his encouragement and support throughout his academic career.