Microbiota and anaphylaxis: emerging insights into immune regulation and clinical implications

Anaphylaxis is a life-threatening systemic hypersensitivity reaction with highly variable clinical expression and unpredictable severity. Increasing evidence suggests that host-microbiota interactions may contribute to interindividual variability in allergic sensitization and effector responses. This review summarizes current mechanistic, preclinical, and emerging human data supporting a role for the microbiota in modulating anaphylaxis risk and severity.

Recent experimental studies demonstrate that gut microbial composition and function influence susceptibility to systemic allergic reactions through effects on immune maturation, epithelial barrier integrity, and mast cell biology. Microbiota-derived metabolites, particularly short-chain fatty acids, can directly suppress mast cell activation and degranulation via epigenetic mechanisms. In parallel, preclinical models indicate that dysbiosis exacerbates anaphylactic responses, whereas microbial restoration attenuates disease severity. Emerging translational evidence further suggests that commensal bacteria may directly metabolize food allergens, reducing IgE-binding capacity and effector cell activation. Human studies, although limited, report associations between microbial signatures, allergen-specific IgE levels, and clinical phenotypes, as well as links between microbiota composition and oral immunotherapy outcomes.

Current evidence supports a biologically plausible role for the microbiota in shaping anaphylaxis susceptibility and severity; however, findings remain largely associative. Future longitudinal and mechanistic studies are needed to establish causality and evaluate the translational potential of microbiota-targeted strategies for the prevention and management of anaphylaxis.