Sympathetic denervation alters pulmonary microbiota diversity and composition in mice

The pulmonary sympathetic nervous system (SNS) regulates airway tone, vascular resistance, and immune responses, yet its role in shaping the lung microbiome remains poorly understood. This study investigated the effects of chemical pulmonary sympathetic denervation (SD) on lung microbial diversity and community structure in mice. Male C57BL/6 mice were randomly assigned to a control group or an SD group that received intrapulmonary 6-hydroxydopamine (6-OHDA) to ablate sympathetic nerve terminals. Lung tissues were analyzed for histopathology, tyrosine hydroxylase (TH), and norepinephrine (NE) levels, and bronchoalveolar lavage fluid (BALF) was analyzed for TNF-α concentrations. Lung tissue microbiota was profiled by 16 S rRNA gene sequencing (V3–V4 regions), processed with QIIME 2/DADA2, and taxonomically assigned using the SILVA 138 database. Alpha- and beta-diversity metrics, amplicon sequence variants (ASVs), and differential taxa were compared between groups. SD significantly reduced TH expression and NE content in lung tissue (P < 0.01), confirming effective denervation, without inducing histological injury or increasing BALF TNF-α. Compared with Ctrl, SD mice exhibited significantly higher species richness and phylogenetic diversity (ACE, Chao1, Observed species, PD whole tree; P < 0.01) but no significant change in Shannon or Simpson indices. Beta-diversity analysis showed clear separation between groups (PERMANOVA, P = 0.007–0.04). Flower plot and taxonomic annotation revealed more unique ASVs and broader phylogenetic representation in SD mice. Differential abundance analysis identified enrichment of Staphylococcus, Pelomonas, and Burkholderiales in the SD group. Pulmonary sympathetic denervation significantly increases lung microbial richness and alters key taxa without triggering overt inflammation, suggesting that SNS activity is an important regulator of pulmonary microbial ecology under resting conditions.