The lung microbiome in childhood-onset severe neuromuscular disease with respiratory insufficiency: rationale, current evidence, and opportunities for oxford nanopore long-read sequencing

Abstract In severe childhood-onset neuromuscular disease (NMD), ventilatory muscle weakness and ineffective airway clearance drive recurrent infections and chronic colonization that is often culture-negative, polymicrobial, or both. The lung microbiome framework offers a unifying model: altered microbial immigration, elimination, and growth can produce dysbiosis with pathobiont expansion and antimicrobial resistance (AMR). We propose that pediatric NMD may follow a distinct developmental trajectory in which early-life secretion stasis, viral insults, and frequent antibiotics perturb immune–microbiome crosstalk during lung growth, potentially “imprinting” long-term community structure. However, NMD-specific airway microbiome data remain sparse because most studies rely on culture or upper-airway sampling. Oxford Nanopore Technologies (ONT) long-read sequencing enables real-time metagenomics with AMR gene detection and can deliver same-day profiles (as short as ~ 6 h from sample to result in optimized workflows), but requires robust low-biomass controls and, in some settings, polishing or hybrid strategies to mitigate higher per-read error. A major limitation of metagenomic sequencing of respiratory samples is the high proportion of host DNA, bacterial reads may account for only about 1–5% of the total sequencing reads. We review microbiome principles relevant to pediatric NMD, summarize current evidence, and outline ONT-enabled study designs and translational priorities.