Gut Bacteriome and Mycobiome Signatures and Differential Allergen-Driven Outcome in Peanut and OVA Anaphylaxis and Their Modulation by Betanin

Abstract Food allergy (FA) pathogenesis is closely associated with perturbations of the enteric ecosystem; however, comparative studies examining how distinct allergen triggers differentially affect the enteric mycobiome (total fungal community residing in the gastrointestinal tract) and the enteric bacteriome (total bacterial community residing in the gastrointestinal tract) remain limited. Mapping these allergen-specific patterns of dysbiosis is critical for understanding the pathogenesis and designing targeted therapies. We investigated betanin, a naturally occurring bioactive compound with potent antioxidant and anti-inflammatory properties as a prophylactic agent capable of resolving allergen-specific dysbiosis and restoring immune homeostasis and intestinal barrier integrity. We established parallel peanut and ovalbumin (OVA) FA mouse models, administered betanin prophylactically across the sensitization and challenge phases, and evaluated its effects on the allergic outcomes. Efficacy was assessed by measuring anaphylactic symptom scores, allergic biomarkers (total IgE), allergen-specific IgE, histamine, and mast cell protease-1 (mMCPT-1), Th1/Th2 cytokine profiles, and their associated transcription factors (GATA3 and T-bet), intestinal barrier integrity markers, and tight junction protein expression. Allergen-specific microbial shifts were characterized by using ITS2 and 16S rRNA amplicon sequencing. Betanin significantly attenuated the anaphylactic symptoms in both models. It suppressed the Th2-driven allergic cascade, evidenced by GATA3 downregulation and concurrent reductions in IL-4, IL-5, IL-13, allergen-specific IgE, histamine, and mMCPT-1. Betanin intervention notably restored intestinal villus architecture, indicating improved intestinal structural integrity, which was further supported by the upregulated tight junction proteins (i.e., claudin-1, occludin, and tight junction protein 1). Furthermore, betanin restored allergic-associated dysbiosis with both mycobiome and bacteriome enriching Lachnospiraceae (a well-known family associated with short-chain fatty acid production) and suppressing pathobionts Desulfovibrio. These results suggest that prophylactic betanin administration attenuated IgE-mediated anaphylaxis in two murine allergen models through coordinated immunomodulation, intestinal barrier structure integrity, and enteric microbiome remodeling.