Next-Generation Probiotics in Allergy Therapy: Scientific Evidence and Clinical Applications.

The global increase in allergic diseases, such as atopic dermatitis, allergic rhinitis, asthma, and food allergies, has become a major public health issue. These diseases typically involve immune dysregulation, including a Th1/Th2 imbalance, increased IgE levels, regulatory T cell (Treg) dysfunction, and epithelial barrier dysfunction. New research has recognised an important role for the gut and mucosal microbiome in regulating immune responses and has prompted interest in the therapeutic utility of probiotics. Probiotics are live microbes that, when given in adequate amounts, confer health benefits, generally such as immunomodulation or restoration of gut barrier function. Traditional probiotics (i.e., Lactobacillus and Bifidobacterium species) reduce allergic inflammation through promotion of Treg differentiation, increases in antiinflammatory cytokines (e.g., IL-10), suppression of Th2 cytokines (e.g., IL-4), and modification of IFNγ. Traditional probiotics also support mucosal barrier function and restore microbial composition by producing short-chain fatty acids (SCFAs), like butyrate, which act directly on Gprotein- coupled receptors and histone deacetylases to suppress inflammation. Next-generation probiotics (NGPs), such as Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis, and some clusters of Clostridia, can provide more targeted effects. These NGPs can secrete anti-inflammatory metabolite compounds, such as polysaccharide A (PSA), which modulate dendritic cells and increase Treg activity, and can promote mucin production to improve gut barrier function. Overall, there are key issues with strain specificity, dose, safety in immunocompromised individuals, and possible regulatory classification issues. Future opportunities may include precision microbiome profiling, synthetic biology, and artificial intelligence-driven strain discovery to develop personalised approaches to allergy immunotherapy.