The Role of Fecal Microbiome Transplantation in Steroid Hyporesponsive Asthma

Abstract

Asthma is a chronic inflammatory airway disease characterized by airflow obstruction, airway hyperresponsiveness, and structural remodeling. Corticosteroids remain the mainstay of asthma therapy; however, a substantial proportion of patients with severe disease develop steroid hyporesponsiveness, limiting therapeutic efficacy and increasing disease burden. Emerging evidence implicates the gut microbiome as a key regulator of systemic immune responses, with growing relevance to asthma pathogenesis and treatment responsiveness. In this study, we investigated whether gut microbiota dysbiosis contributes to steroid hyporesponsive lung inflammation and whether fecal microbiota transplantation (FMT) can restore steroid responsiveness. Using a steroid-hyporesponsive asthma model, we demonstrate that the disease is associated with significant gut microbial dysregulation, characterized by reduced microbial diversity and depletion of immunoregulatory taxa. FMT partially restored gut microbial diversity, normalized community structure, and selectively replenished beneficial commensal bacteria, including Akkermansia muciniphila and Faecalibacterium prausnitzii, while suppressing pathogenic taxa. Importantly, restoration of gut microbial balance was associated with attenuation of lung inflammation and improved steroid responsiveness. These findings support a functional gut-lung axis in steroid hyporesponsive asthma and identify modulation of gut microbiota as a potential therapeutic strategy. Incorporating microbiota-directed interventions such as FMT may represent a novel adjunct approach for the management of refractory steroid-hyporesponsive asthma.