Gut bacterial lactate stimulates lung epithelial mitochondria and exacerbates acute lung injury.

Summary

Using gnotobiotic mice, lung epithelial cell assays, and ARDS patient metabolomics, the authors show that gut bacterial metabolites—specifically lactate—stimulate mitochondrial activity in lung epithelium and worsen acute lung injury. Colonization of germ-free mice induced lung mitochondrial gene programs, linking the gut–lung axis to ARDS pathobiology.

Key Findings

• Gut microbiota colonization of germ-free mice increased lung mitochondrial gene expression.
• Gut bacterial metabolites, notably lactate, stimulated mitochondrial activity in lung epithelial cells.
• Re-analysis of a large ARDS metabolomics dataset supported links between bacterial metabolites and lung injury severity.

Clinical Implications

While preclinical, findings suggest testing microbiome modulation or lactate transport inhibition to mitigate lung injury. Metabolic profiling may identify at-risk patients with microbiome-driven mitochondrial dysregulation.

Limitations

• Preprint not peer-reviewed; details on specific taxa and causal human evidence are limited in the abstract
• Translational relevance and therapeutic strategies require validation in clinical studies

Future Directions

Identify causative taxa and metabolite fluxes, test lactate transport/metabolism inhibitors in vivo, and validate microbiome–mitochondria signatures in prospective ARDS cohorts.