This study aimed to examine the relationship between gut microbiome diversity, immune modulation, and allergen immunotherapy (AIT) effectiveness in patients with allergic rhinitis (AR). A prospective cohort study was conducted on 450 participants: 300 adult patients with allergic rhinitis, who were eligible for AIT, and 150 healthy controls. The Total Nasal Symptom Score (TNSS) and the Rhinitis Quality of Life Questionnaire (RQLQ) were used to assess symptom severity and the impact of AR on daily life. Blood and stool samples were collected at baseline and after six months of AIT for microbiome analysis. The stool samples were analyzed with the 16S rRNA gene V4 region, followed by sequencing on the Illumina MiSeq platform. The microbial composition and diversity were assessed using the QIIME2 pipeline, and taxonomic assignments were made using the SILVA reference database. Short-chain fatty acids (SCFAs) were quantified using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Flow cytometry was used to quantify T-regulatory cells (Tregs). Cytokine levels (IL-10, IL-4, IFN-γ) were measured using enzyme-linked immunosorbent assays (ELISA). Allergic rhinitis patients and healthy controls were matched for age and weight; however, AR patients had a significantly higher BMI (P = 0.0006). Baseline TNSS and RQLQ scores were significantly worse in AR patients compared to controls (P < 0.001), but both improved significantly after six months of AIT (P < 0.001). AR patients demonstrated reduced gut microbial diversity (P = 0.028), distinct microbial profiles, and lower levels of SCFAs, indicative of dysbiosis. Immune markers in AR patients revealed lower levels of IL-10 and T-regulatory cells (P < 0.05, P < 0.001) and higher levels of IL-4 and Th2 cells (P < 0.001). Proteobacteria were associated with a decrease in TNSS and an improvement in RQLQ scores (P < 0.05). Allergen immunotherapy improves symptoms and quality of life in AR patients. This may potentially influence immune and microbial imbalances. Proteobacteria may have a protective role in allergic rhinitis, suggesting their potential as a biomarker or therapeutic target in the management of AR.
