Introduction: Communication between gut microbiota and extraintestinal organs is increasingly recognized, yet elucidation of relevant translocation mechanism(s) remain unclear. The vagus nerve has been reported to translocate proteins from the stomach to extraintestinal sites, such as the brain.

Objectives: To discern the capacity of the vagus nerve to serve as a conduit of viable gut flora, and if possible to discern if physiologic consequences on lung severity are present. 

Materials and Methods: To investigate this process, kanamycin-resistant, green fluorescent protein–expressing Escherichia coli (GFP-E. coli) were orally gavaged into germ-free (GF) and wild-type (WT) C57BL/6 mice whose organs were harvested five minutes later. Confocal microscropy was used to visualize bacteria within the vagus nerve.

Results: Qualitative and quantitative analyses of organ bacterial cultures revealed high loads in the stomach and lungs, followed by the heart, stool and peripheral muscles. Bacteria were absent from the blood. No bacteria were detected in non-gavaged GF mice. Similar extraintestinal translocation patterns were observed in wild-type (WT) C57BL/6 mice following GFP-E. coli gavage. Confocal microscopy and culture of the vagus nerve revealed GFP-E. coli. Metagenomic analysis of stool, lung, heart, vagus nerve, and muscle samples from non-gavaged WT mice demonstrated significant genetic overlap. Remarkably, subdiaphragmatic vagotomy performed prior to GFP-E. coli gavage resulted in marked reductions of bacterial recovery in the lungs and other extraintestinal organs, except muscle. Furthermore, vagotomy significantly reduced lung fibrosis in WT mice following intranasal bleomycin administration. In cancer patients, vagotomy inhibited forced vital capacity reductions, following lobectomy. 

Conclusions: These findings identify the vagus nerve as a literal gut–lung axis that facilitates viable bacterial translocation and influences lung severity.