Changes in respiratory and gut microbiota in asthma and depression associate with disease markers

Asthma is heterogeneous and frequently accompanied by depression, affecting disease mechanisms and management. Both asthma and depression have been associated with inflammation and microbiota alterations, but their combined impact on microbial compositions remains unclear. Our exploratory study analyzed lung and gut microbiota in patients with asthma and depression to identify associations between microbiota composition and disease markers. This cross-sectional study included 20 healthy controls, 20 patients with asthma, and 20 patients with asthma and comorbid depression. Participants underwent clinical characterization and assessment of asthma control, depression, anxiety, and perceived stress. Induced sputum and fecal samples were collected for microbiota analysis, and inflammatory cytokines were measured in serum and sputum. Microbial profiling was performed using 16S rRNA gene sequencing. Lung function and FeNO levels were comparable between all groups. Asthma control scores were lower, and psychological scores were significantly higher in patients with asthma and comorbid depression compared with asthma alone and controls. Despite similar alpha and beta diversity across groups, sputum and fecal microbiota, particularly of healthy controls and comorbid patients, significantly differed in genus-level taxonomic composition. Correlation analyses demonstrated associations between clinical and psychological parameters and microbial profiles, including a consistent negative correlation between psychological scores and Neisseria abundance in both sputum and fecal samples. Asthma with comorbid depression is associated with distinct alterations in respiratory and gut microbiota, including reduced Neisseria perflava abundance correlating with psychological symptom severity. IMPORTANCE Asthma and depression frequently coexist, yet the potential contribution of microbial alterations to this comorbidity remains poorly understood. Because both respiratory and gut microbiota have been implicated in immune regulation and disease pathophysiology, characterizing microbiota patterns associated with asthma and depression may provide new insights into the biological links between these conditions. In this exploratory study, we investigated respiratory and gut microbiota in individuals with asthma, with and without comorbid depression, and healthy controls. Genus-level community composition differed between groups, particularly between controls and patients with asthma and depression. Notably, reduced abundance of Neisseria perflava in sputum and fecal samples was consistently associated with greater psychological symptom severity. These findings suggest that asthma accompanied by depression is associated with distinct alterations in microbial communities at multiple body sites. Further studies are warranted to determine whether such microbiota–psychological associations contribute to disease mechanisms or may serve as biomarkers of asthma–depression comorbidity.