Aspartame and asthma: immunomodulatory effects on airway inflammation

BACKGROUND AND OBJECTIVE: Asthma is a heterogeneous inflammatory airway disease influenced by genetic and environmental factors, including diet. Aspartame, a widely used artificial sweetener, has been implicated in immunometabolic changes that may affect asthma risk, but the potential role evidence remains limited. We aimed to examine the association between aspartame intake and asthma outcomes using integrated human analyses and complementary animal experiments. METHODS: Human data were obtained from 1021 adolescents in the Taiwan Puberty Longitudinal Study. Aspartame consumption, assessed using a validated food frequency questionnaire, was categorized as none, low, or high based on median intake. Asthma status was determined based on physician diagnosis and symptom history. In parallel, BALB/c mice were sensitized with house dust mite (HDM) extract and administered oral aspartame at 15, 30, or 60 mg/kg/day for 10 weeks. Immunological, microbiome, metabolic, and histopathological parameters were evaluated. RESULTS: Low aspartame consumption was significantly associated with higher odds of asthma (odds ratio = 2.852; 95% confidence interval: 1.038-8.014; p = 0.0369). In mice, aspartame exposure increased serum IgE levels, airway inflammation, and MMP-12 and MCP-1 expression. Although lung function changes were not statistically significant, histological analyses revealed more pronounced goblet cell hyperplasia, peribronchial collagen deposition, and eosinophilic infiltration, especially in the 60 mg/kg group. Aspartame also reduced microbial α-diversity and altered microbial composition. Short-chain fatty acids profiling revealed significantly decreased isobutyric, hexanoic, and heptanoic acid levels in aspartame-treated mice. CONCLUSIONS: Aspartame intake exacerbates asthma-related immunological, microbial, and histological disturbances.