Multi-target Effects of Short-Chain Fatty Acids for Obesity-Related Asthma: Interventional Potential and Challenges

In recent years, the prevalence of obesity and asthma has risen steadily, emerging as two major chronic diseases threatening public health. These conditions exert mutual promotion and may induce pathological superposition effects in obesity-related asthma. Obesity-related asthma represents a distinct asthma phenotype, with pathogenesis involving chronic low-grade inflammation, metabolic dysregulation, mechanical constraints, and genetic predispositions. Critically, four core components, including adipose dysfunction with metabolic dysregulation, gut microbiota dysbiosis with intestinal barrier impairment, systemic chronic inflammation, and pulmonary inflammation with airway hyperresponsiveness, interlock into a self-reinforcing cycle that synergistically amplifies disease progression. Accordingly, obesity-related asthma exhibits a greater clinical burden than classical asthma, including more severe symptoms, higher exacerbation rates, and poorer therapeutic responsiveness. As key metabolites derived from gut microbiota, short-chain fatty acids (SCFAs) demonstrate potential to disrupt this pathological cycle in obesity-related asthma through anti-inflammatory actions, immune-metabolic modulation, and epithelial barrier protection. Furthermore, SCFA levels can be effectively modulated through dietary interventions, microbial preparation supplementation, and fecal microbiota transplantation, positioning them as promising translational targets for obesity-related asthma.