Modulation of the microbiome by sublingual allergen immunotherapy: current insights and clinical implications

Abstract Background Specific allergen immunotherapy (AIT) represents the only causal treatment for allergic diseases capable of modifying the natural disease trajectory and inducing long-term allergen tolerance. Its sublingual form (SLIT) has emerged as a safe and highly effective alternative to conventional subcutaneous administration. In recent years, scientific interest has increasingly focused on the complex interplay between SLIT and the human microbiome. Methods We conducted a targeted literature search across four major electronic databases (PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library) from January 2012 to February 2026. Applying strict inclusion criteria, a narrative review approach underpinned by a systematic search strategy was utilized to qualitatively synthesize 41 peer-reviewed articles evaluating baseline dysbiosis, post-SLIT microbial shifts, and adjuvant interventions. Results A growing body of evidence suggests that the therapeutic efficacy of SLIT is associated with alterations in microbial communities across the oral–gut–immune axis. However, recent clinical data present a more nuanced picture, indicating that clinical efficacy can occur without complete microbial normalization. Integrating these insights with established immunology highlights the microbiome’s role as an epigenetic stabilizer in maintaining rather than merely initiating long-term allergen tolerance. Conclusion Shifting toward precision allergology, we critically appraise the search for predictive baseline biomarkers, expose the severe methodological heterogeneity limiting current probiotic adjuvant trials, and underscore the unexplored potential of dietary interventions (e.g., fermentable fibers) to harness endogenous tolerogenic metabolites.