Hospital bug jumps from lungs to gut, raising sepsis risk

A hospital-acquired bacterium that causes serious infections can move from the lungs to the gut inside the same patient, raising the risk of life-threatening sepsis, new research reveals.

Published today (25 November) in Nature Communications, researchers at the Wellcome Sanger Institute analysed DNA data taken from hospital patients to understand movement of the bacterium, Pseudomonas aeruginosa (P. aeruginosa) within individuals.

The research sheds light on how lung infections can result in the spread of a major disease-causing bacterium between multiple parts of the body, increasing the risk of sepsis in vulnerable patients. The insights from the study may inform future strategies for hospitals to track and prevent sepsis-related deaths.

P. aeruginosa is a common bacterium that can cause disease in humans, plants and animals. It is a major cause of hospital-acquired infections and can result in conditions such as pneumonia, ear infections, urinary tract infections, and wound infections.

The bacterium is also known to be one cause of sepsis. Sepsis occurs when the body responds improperly to an infection. The infection-fighting process starts to attack the body, causing some organs to shut down. It is a life threatening condition and in the UK, there are 48,000 sepsis related deaths each year and five related deaths occur every hour.¹

In a previous study,² research has shown that P. aeruginosa has moved from the gut to the lungs in an individual intensive care unit (ICU) patient, bringing to light its ability to move and colonise other body sites. However, how often this happens, and in which direction the bacteria tend to spread, have remained unclear.

In a new study, researchers at the Sanger Institute analysed metagenomic³ sequencing data from 256 hospital patients in Italy.⁴ They used these data to understand where P. aeruginosa starts to colonise and in what direction the bacterium moves throughout the body.

Of the 84 patients where P. aeruginosa genomes could be recovered, the team found 27 cases where the same bacterial clone (cells that are identical in their DNA) appeared across multiple body sites. This indicates that most of these infections were not acquired repeatedly from the hospital environment, but most were established and colonised by a single clone over time and spread within the patient’s own body. Additionally, P. aeruginosa infection in ICU patients was significantly more common than in patients on other wards.

By building family trees of P. aeruginosa genomes, the team predicted that most strains that had spread originated in the lungs. This suggests that infections most likely move from the lungs to the gut, where P. aeruginosa can establish long-term colonisations. The researchers propose that naturally swallowing sputum – a mixture of saliva and mucus from the lungs – that may contain P. aeruginosa could be a likely route of gut colonisation. They also did not find P. aeruginosa in nasal samples only, suggesting that it must be present elsewhere in the body first and the nose acts as a spillover site rather than a stable colony site. 

The researchers also detected frequent DNA changes in genes associated with antimicrobial resistance (AMR), regardless of where the bacteria are found in the body. These DNA changes will make treatment considerably more difficult.

Ultimately, the findings have significantly expanded on a small body of existing knowledge about within-person movement of a dangerous bug. Colonisation of P. aeruginosa within the lungs should therefore be considered a risk-factor for sepsis that begins in the gut in patients who are particularly vulnerable to this life-threatening condition.

Dr Lewis Fisher, first author at the Wellcome Sanger Institute, said: “We found that most patients carried the same strain of P. aeruginosa across multiple samples showing that once this bacterium establishes itself, it tends to persist rather than being replaced by new infections. This persistence helps explain why the bug can be so difficult to eradicate in hospital settings.”

Dr Ron Daniels, Founder and Chief Medical Officer at the UK Sepsis Trust, said: "Notoriously difficult to eradicate, Pseudomonas infections are a major issue in our Intensive Care Units, particularly in patients with weakened immune systems, and a major cause of sepsis. This new research serves to enhance our understanding of this organism which can only be good for our patients now and in the future — it highlights how little we know about disease-causing bugs and their behaviours.”

Professor Jukka Corander, co-author at the Wellcome Sanger Institute and the University of Oslo, Norway, said: “We also saw rapid genetic changes in antibiotic resistance genes, no matter where the bacterium was found in the body. This highlights how quickly P. aeruginosa can adapt, making it increasingly hard to treat and control in intensive care environments.”

Dr Josie Bryant, senior author at the Wellcome Sanger Institute, said: “Our findings show these bacterial infections often spread inside patients’ own bodies, typically from the lungs to the gut. Recognising this hidden movement is key to improving how hospitals monitor and prevent sepsis in vulnerable patients.”

ENDS