Multi-Omics Reveals Aberrant Phenotypes of Respiratory Microbiome and Phospholipidomics Associated with Asthma-Related Inflammation.

Respiratory microbiota and lipids are closely associated with airway inflammation. This study aimed to analyze the correlations among the respiratory microbiome, the airway glycerophospholipid-sphingolipid profiles, and airway inflammation in patients with asthma. We conducted a cross-sectional study involving 61 patients with asthma and 17 healthy controls. Targeted phospholipidomics was performed on exhaled breath condensate (EBC) samples, and microbial composition was analyzed via the 16S rDNA sequencing of induced sputum. Asthma patients exhibited significant alterations in the EBC lipid profiles, with reduced levels of multiple ceramides (Cer) and glycerophospholipids, including phosphatidylethanolamine (PE) and phosphatidylcholine (PC), compared with healthy controls. These lipids were inversely correlated with the sputum interleukin-4 (IL-4) levels. Microbiome analysis revealed an increased abundance of and in asthma patients, both positively associated with IL-4. Correlation analysis highlighted a potential interaction network involving PA, PE, ceramides, , , , and . Specific alterations in airway microbiota and phospholipid metabolism are associated with asthma-related inflammation, supporting the concept of a microbiota-phospholipid-immune axis and providing potential targets for future mechanistic and therapeutic studies.