Pathogen-oriented mNGS is not equivalent to microbiome profiling: interpreting BALF mNGS diversity in ARDS.

Abstract

Gao et al. provide valuable data-linking bronchoalveolar lavage fluid metagenomic next-generation sequencing with inflammatory subphenotypes of acute respiratory distress syndrome. We highlight three issues relevant to interpretation: an apparent inconsistency concerning exclusion of samples with no micro-organisms detected, use of a pathogen-oriented workflow for community-level ecological inference, and the distinction between detection yield and diagnostic performance without an independent reference standard. Clarification of sample eligibility, sensitivity analysis including technically valid samples reported as negative by sequencing, and confirmation that sequencing and bioinformatic procedures are validated for quantitative microbiome analysis would strengthen interpretation.