ABSTRACT

Background:
Obesity-related asthma (OB-AS) is characterized by a suboptimal response to standard therapies and an elevated risk of refractory asthma. While caffeine demonstrates protective associations against both asthma and obesity, its role in OB-AS remains unclear.

Methods:
A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (2007-March 2020). Weighted multiple regression and restricted cubic spline models were employed to assess the relationship between caffeine intake and OB-AS risk. A two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal relationship between coffee consumption and OB-AS risk, followed by a mediation analysis to examine the gut microbiota's role. Additionally, core genes of caffeine's effect on OB-AS were identified to explore underlying biological mechanisms.

Results:
After screening, 3751 asthma cases and 27 935 non-asthma controls were included. Caffeine intake was inversely correlated with OB-AS risk (odds ratio [OR] = 0.83, 95% confidence interval [CI] = 0.70-0.97, P = 0.020). A significant non-linear association between caffeine intake and OB-AS risk was observed among males (P for non-linearity = 0.009). MR analysis confirmed a causal association between coffee consumption and reduced OB-AS risk (inverse-variance weighted method: OR = 0.133, 95% CI = 0.025-0.712, P = 0.019). Mediation analysis revealed that Collinsella mediated 14.9% of this association. We identified 42 core genes associated with caffeine's effect on OB-AS, with enrichment observed in corticosteroid response pathways.

Conclusions:
Caffeine intake demonstrates a protective effect against OB-AS risk, partially mediated by Collinsella. It is hypothesized that caffeine might influence OB-AS via corticosteroid response pathways.

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