Abstract Introduction The metabolism of microbes plays an important role in defining the metabolic landscapes within the respiratory tracts. Sulfur metabolism by the gut microbiome modulates sulfur metabolite levels, which are linked to antioxidant capacity in the gastrointestinal tract. Commensal organisms, such as Porphyromonas and Desulfobacter, within the oral cavity can metabolize reactive sulfur species, including sulfate and sulfide. Some of these bacteria are found in the lower airway microbiome possibly though microaspiration. We hypothesize sulfur metabolism and microbes capable of sulfur metabolism are enriched in the lower airway of patients with COPD compared to smoker controls (SC), potentially affecting antioxidant capacity and lung injury due to oxidative stress. Methods Lower airway bronchoalveolar lavage (BAL) samples were obtained from 55 patients with mild COPD and SC. Metatranscriptomic and untargeted metabolomic profiles were obtained from these samples. Only KEGG-annotated metabolites were analyzed. Pathway analysis was performed using MetaboAnalyst based on KEGG metabolic pathways. To compare metatranscriptomic profiles between the highest and lowest quartiles of sulfate abundance, principal component analysis using the Bray-Curtis dissimilarity index and differential analysis with edgeR were performed. Results 266 unique KEGG annotated metabolites were identified in BAL samples. There were statistically significant differences in beta-diversity in lower airway metabolic profiles between COPD and SC (Figure 1A). Sulfur metabolism was most enriched metabolic pathway in the lower airways of COPD patients (Figure 1B). Sulfate contributed most to the separation between lower airway metabolomic composition of COPD and SC. Separating sulfate levels into quartiles, the lowest quartile of sulfate had higher prevalence of COPD while the highest quartile had higher prevalence of SC subjects (Figure 1C). Comparing samples in the highest quartile of sulfate levels to the lowest quartile, a statistically significant difference was observed in the taxonomic composition and functional annotation of the metatranscriptome. Notably, oral commensals, such as Streptococcus dysgalactiae and Desulfobulbus oralis, were enriched in samples with the lowest sulfate levels (Figure 1D). Looking at microbial functions, many genes involved in sulfur metabolism, such as aprA and asrC, were enriched in these samples. Conclusions Lower airway sulfur metabolism varies between COPD and smoker controls. Differences in sulfur metabolites in the lower airway may result from enrichment of oral commensals influencing microbial sulfur metabolism. Future studies should examine whether enrichment of lower airway oral commensals is associated with altered sulfur metabolism and modulation in oxidative stress, a key driver of inflammatory injury and COPD. This abstract is funded by: NIH
Wong et al. (Fri,) studied this question.