Metabolic pathways from the gut metatranscriptome are associated with COPD and respiratory function in lung cancer patients.

INTRODUCTION

Changes in the human gut microbiome have been linked to various chronic diseases, including chronic obstructive pulmonary disease (COPD). While substantial knowledge is available on the genomic features of fecal communities, little is known about the microbiome's transcriptional activity. Here, we analyzed the metatranscriptomic (MTR) abundance of MetaCyc pathways, SuperPathways, and protein domain families (PFAM) represented by the gut microbiome in a cohort of non-small cell lung cancer (NSCLC) patients with- or without COPD comorbidity.

METHODS

Fecal samples of 40 NSCLC patients with- or without COPD comorbidity were collected at the time of diagnosis. Data was preprocessed using the Metaphlan3/Humann3 pipeline and BioCyc to identify metabolic SuperPathways. LEfSe analysis was conducted on Pathway- and PFAM abundance data to determine COPD- and non-COPD-related clusters.

RESULTS

Key genera , and were significantly more active transcriptionally compared to their metagenomic presence. LEfSe analysis identified 11 MetaCyc pathways that were significantly overrepresented in patients with- and without COPD comorbidity. According to Spearman's rank correlation, Smoking PY showed a significant negative correlation with , and , and a significant positive correlation with and , whereas forced expiratory volume in the first second (FEV1) showed a significant negative correlation with and a significant positive correlation with . Furthermore, COPD patients showed a significantly increased MTR abundance in ~60% of SuperPathways, indicating a universally increased MTR activity in this condition. FEV1 showed a significant correlation with , , and . Taxonomic analysis suggested a more prominent MTR activity from multiple species, and than expected from their metagenomic abundance. Multiple protein domain families (PFAMs) were identified as more associated with COPD, , and , contributing the most to these PFAMs.

CONCLUSION

Metatranscriptome analysis identified COPD-related subsets of lung cancer with potential therapeutic relevance.