Rebalancing the inflammatory niche in allergic rhinitis ".

Allergic rhinitis (AR) may be driven in part by cross-talk between resident microbiota, microbe-derived small molecules, and tissue-resident group 2 innate lymphoid cells (ILC2s). In this review we focus on defined signaling axes by which Traditional Chinese Medicine (TCM) can influence that network: (1) microbially produced short-chain fatty acids (SCFAs), particularly butyrate, suppress ILC2 proliferation and type-2 cytokine output primarily via HDAC inhibition that downregulates the lineage transcription factor GATA3; receptor-dependent effects via the SCFA sensors FFAR3 (GPR41), FFAR2 (GPR43), and GPR109A (HCAR2) also occur in some cell types and tissues, and can engage β-arrestin/ERK or AMPK-linked pathways depending on cell context. In purified ILC2s, ex-vivo reductions in GATA3 and IL-13/IL-5 are observed at low micromolar to several hundred micromolar butyrate (human ILC2 ≈ 10 μM; murine ex-vivo ILC2 ≈ 200 μM), while viability is generally preserved below ∼1 mM, indicating a physiologically plausible dose window for metabolite-driven modulation; (2) microbially modified secondary bile acids alter mucosal immune tone and epithelial function via FXR and TGR5 signaling; and (3) microbial tryptophan metabolites (indoles) act as aryl hydrocarbon receptor (AhR) ligands that preserve epithelial integrity and shape ILC3/ILC2 balance. We review preclinical and emerging clinical data suggesting that selected TCM formulas and phytochemicals (e.g., Gegen Qinlian Decoction, Astragalus polysaccharides, berberine, baicalin/baicalein, glycyrrhizin) are associated with (a) remodeling of gut and airway microbial communities and increases in SCFA or beneficial bile/indole pools in preclinical and some human studies, (b) measurable rises in systemic or luminal SCFAs in several models and limited human cohorts, and (c) direct attenuation of epithelial alarmin (TSLP/IL-33) signaling in cellular and animal models. Where human data exist, causality remains unproven and further mechanistic clinical investigation is required. Together these actions provide testable, mechanism-based routes to suppress ILC2 activation and restore mucosal homeostasis in AR. We explicitly link TCM-driven microbiome/metabolome changes to canonical molecular mediators (HDAC, GPR41/43, FXR/TGR5, AhR, TSLP/IL-33, HMGB1) to facilitate mechanistic trial design that measures taxa → metabolite → receptor/epithelial → ILC2 causal chains.