First evidence that antibiotic resistant bacteria can travel from the gut to the lung, increasing risks of deadly infections

A new study released today in Nature Communications from the Department of Biology, University of Oxford has found the first direct evidence of antibiotic resistant bacteria migrating from a patient’s gut microbiome to the lungs. Applying the findings of this study could save lives, as it highlights the importance of preventing pathogenic bacteria from translocating from the gut to other organs where they can cause serious infections.

The study was conducted on a patient that carried the bacterium Pseudomonas aeruginosa as part of their gut microbiome.  This species is one of the leading causes of infections in hospitals, and one that is particularly good at resisting antibiotics. Whilst P. aeruginosa is generally not considered to be dangerous when it is embedded in a healthy gut microbiome, it can cause serious infections in the lungs of hospitalized patients.

A false colour microscope image of a sample of lung infected with AMR Pseudomonas aeruginosa

 

During their stay in hospital the patient was treated with the antibiotic Meropenem for a suspected urinary tract infection (UTI). Meropenem treatment caused non-resistant bacteria in the gut and lung to be killed off, and antibiotic resistant mutants of P. aeruginosa were able to grow and proliferate.

P. aeruginosa was then found to translocate from the gut to the patient’s lungs during antibiotic treatment, where it evolved even higher levels of antibiotic resistance.

The findings of this study suggest that eliminating AMR pathogens from the gut microbiome of hospitalized patients could help to prevent serious infections, and it highlights how antibiotic use can have profound impacts on bacteria that are not actually the target of antibiotic treatment.

Researchers tested the patient throughout their time in hospital to track the duration of their infection with P. aeruginosa. They used a genetic approach, creating a time-calibrated bacterial family tree that allowed them to analyse the progression and location of infection, plus its evolution. They also found high genetic diversity in the gut, which also suggests that the microbiome may be a reservoir for AMR to arise.

Fortunately, the patient in this case had an immune response to the AMR bacteria in their lungs, preventing the infection from causing pneumonia. However, many people in critical conditions, particularly over winter, have a weakened immune system, meaning the body is less able to fight off disease. AMR policies often focus on reducing infection from external sources, but understanding how AMR can develop and spread within a patient is just as vital.

The researchers now intend to assess how frequently gut to lung bacterial translocation occurs in vulnerable patients by collecting samples from a much larger cohort.

Professor Craig MacLean said:

‘There is a clear need to develop new approaches to the challenges that antimicrobial resistance presents. Our study shows how gut-lung translocation and antibiotic use can combine to drive the spread of AMR within a single patient. Insights such as this are needed in order to develop new interventions to prevent resistant infections. For example, our study highlights a potential benefit of eliminating AMR bacteria like Pseudomonas aeruginosa from the gut microbiome of hospitalized patients, even when these bacteria are not actually causing infection.’

‘AMR pathogens can be difficult to eliminate from patients once they have become established, and our work also underscores the importance of avoiding unnecessary antibiotic use, and in developing antibacterial treatments that only target the bacteria that are actually causing an infection.’

To read more about this research, published in the Nature Communications, please visit: https://www.nature.com/articles/s41467-022-34101-2.