Meta-omics profiling of the gut-lung axis illuminates metabolic networks and host-microbial interactions associated with elevated lung elastance in a murine model of obese asthma

We evaluated nitro-oleic acid as a host- and microbial-targeted treatment intervention for obesity-associated asthma. Allergic airway disease was induced using house dust mite and cholera toxin adjuvant in C57BL6/J mice with diet-induced obesity to model obesity-associated asthma. Mice were treated with either glycerol trioleate vehicle (n = 11) or 9,10-nitro-oleic acid (n = 11) via gavage, followed by allergen challenge 3 hours later. Controls included a mock sensitization group (n = 12) that only received adjuvant during sensitization and a group of naive obese mice (n = 7). Lung function was measured by flexiVent following a week of nitro-oleic acid treatment and allergen challenge. 16S rRNA gene (from DNA, taxa presence) and 16S rRNA (from RNA, taxa activity) sequencing were performed on stool samples collected from mice on the day of lung function measurement. Stool RNA and DNA were isolated using ZymoBIOMICS DNA/RNA Miniprep kit, and cDNA was synthesized with the SuperScript IV VILO kit. 16S rRNA amplicons were run on Illumina MiSeq. Targeting both the host and gut microbiota, NO2-OA attenuated airway inflammation, improved lung elastance, and modified the gut microbiome