Bronchiectasis is a chronic lung disease that causes inflammation, excessive mucus production and lung damage. Recent research suggests that gut bacteria, particularly Eggerthella lenta, may play a role by producing a compound that weakens immune cells and makes infections worse. 

The findings, published in Science Translational Medicine, suggest that targeting E. lenta or boosting neutrophil function may lead to new treatment strategies for bronchiectasis and related lung diseases.

Scientists have known that infection with Pseudomonas aeruginosa is a major cause of worsening symptoms of bronchiectasis. But while treatments that target Pseudomonas infections can help patients, other factors, including gut bacteria and the immune system, may contribute to the disease. 

To explore the link between the gut microbiota and bronchiectasis, researchers led by Le-Le Wang at Tongji University in Shanghai, China, analyzed blood, stool and other body samples from 41 people with the condition and 29 healthy individuals. The team also performed fecal microbiota transplants in mice.

Worsen infection

Mice first received antibiotics to clear their gut bacteria, then they were given fecal samples from either people with bronchiectasis or healthy donors before being infected with Pseudomonas aeruginosa in their lungs. 

Animals receiving stool from bronchiectasis patient showed worse lung infections, more lung damage and stronger immune responses than those receiving stool from healthy donors. This finding suggests that gut bacteria can worsen lung infections in bronchiectasis, the researchers say.

People with bronchiectasis had more harmful bacteria, especially Eggerthella lenta, in their guts. The amount of E. lenta was higher in patients with more severe disease and was associated with increased Pseudomonas aeruginosa in the lungs.

Immune cells

To test the idea that E. lenta could worsen infections, the researchers gave the bacterium to mice before infecting them with P. aeruginosa. These mice had worse lung damage, more bacteria and higher inflammation compared to animals that weren’t given E. lenta. 

Further experiments showed that E. lenta produces TUDCA, a compound that weakens the function of immune cells called neutrophils, making lung infections worse. However, treating neutrophils with metformin restored their bacterial-killing ability, the researchers found.

The findings offer evidence of a link between the gut and the lungs, but more research is needed to understand how E. lenta produces TUDCA and how metformin contributes to treating infections, the authors say.