Interactions Between the Microbiome and Pharmacotherapy of Allergic Diseases: Current Evidence and Knowledge Gaps

The gut microbiota plays an important role in immune homeostasis, allergic disease pathogenesis, and drug metabolism, potentially influencing therapeutic efficacy and safety. Conversely, pharmacotherapy may modify gut microbial composition and function, creating bidirectional host–drug–microbiome interactions that remain incompletely understood. This narrative review summarises current evidence on interactions between the microbiome and therapies for allergic diseases, focusing on antihistamines, corticosteroids, leukotriene receptor antagonists, and biologic agents. Evidence is evaluated from two complementary perspectives: an exposure axis, relevant mainly to orally administered drugs, and a response axis, particularly applicable to biologic therapies. Direct microbial biotransformation has been demonstrated most convincingly for glucocorticoids, with the organosteroid reductase ABC (OsrABC) pathway of Clostridium steroidoreducens reducing systemic prednisolone exposure in a gnotobiotic model. For H1-antihistamines and leukotriene receptor antagonists, evidence remains limited and inconsistent. The microbiota may also indirectly influence treatment outcomes through effects on epithelial barrier integrity, microbial metabolite production, and immune regulation. Although anti-allergic therapies can alter gut, airway, and skin microbial communities, no validated microbiome signature currently predicts treatment efficacy or safety. Future prospective studies integrating microbiome, metabolome, pharmacokinetic, pharmacodynamic, and clinical data are needed to establish reliable biomarkers and support personalised pharmacotherapy for allergic diseases.