The nasal-oral microbiome axis in allergic rhinitis: environmental triggers, microbial dysbiosis, and immune dysregulation

Allergic rhinitis (AR) is a common chronic inflammatory disease, which affects about 400 million people around the world. The role of the upper airway microbiota in the development of AR has recently emerged and seems to be an important player in its pathology, but there are still no detailed mechanistic models that incorporate exposure to the environment, dysbiosis of microbes or dysregulated immunity as a whole. In this review we summarize the state of the art about the microbiome nose-mouth connection in AR to understand how environmental stimuli change the microbiota composition as well as how an imbalance can induce allergy-related inflammation. This review follows a narrative approach. Literature was identified through systematic searches of PubMed, Web of Science, and Scopus databases (up to March 2025) using the following key terms and their combinations: “allergic rhinitis’, “nasal microbiome”, “oral microbiome”, “dysbiosis”, “epithelial barrier”, ’short-chain fatty acids’, “Th2 inflammation”, and “probiotics”. Inclusion criteria encompassed original research articles, systematic reviews, and meta-analyses published in English; conference abstracts, case reports, and purely non-human studies were excluded unless they provided mechanistic insights not available from human data. Environmental exposures substantially alter upper airway microbial communities. Air pollutants such as PM₂.₅ and diesel exhaust particles (DEP) damage epithelial tight junction proteins via reactive oxygen species (ROS), increasing nasal permeability. DEP additionally functions as an immune adjuvant by promoting pro-Th2 immune polarization. Antibiotic treatment during early childhood may affect GI tract development by altering resident bacterial populations, being considered as a strong risk factor for developing AR. On the other hand, farm exposure and microbial diversity provide protection by enhancing regulatory T cell induction. AR patients exhibit characteristic nasal dysbiosis, including overgrowth of Staphylococcus aureus and Moraxella catarrhalis alongside depletion of protective commensals such as Dolosigranulum pigrum and Corynebacterium spp. This dysbiosis disrupts the epithelial barrier, triggering alarmin release (TSLP, IL-25, IL-33) and amplifying type 2 inflammation. The oral microbiota also contributes via the oral-nasal-pulmonar y axis whereby periodontal pathogens are pro-inflammatory while commensals have immunomodulatory roles. Mechanistically, microbiome-derived metabolites—especially short chain fatty acids and tryptophan derivatives—regulate the immune system via G protein-coupled receptors, histone deacetylase inhibition, and aryl hydrocarbon receptor activation. Dysbiosis promotes Th2 polarization, Treg/Th17 imbalance, and the activation of ILC2s, whereas neuro-immune interactions via TRPV1/TRPA1 enhance neurogenic inflammation. Translation to clinical opportunity: Microbiome based diagnostic biomarker; Probiotic (nasal/oral); Prebiotics; postbiotics, and engineered bacteria. Multi-omics based precision medicine using ML to stratify patient and tailor intervention. In summary, this review offers an insight into the theory of the microbiome-immunology interplay in AR as well as new avenues to consider regarding treatment of this condition through the nasal-oral microbiota axis.