Emerging insights into the gut-lung axis continue to open new possibilities for managing chronic respiratory diseases, from cystic fibrosis (CF) in the youngest patients to chronic obstructive pulmonary disease (COPD) in older adults. Despite growing evidence linking gut health to respiratory disease pathogenesis, these findings are not yet ready for routine clinical application. Still they underscore the value of discussing diet and nutrition with patients as part of broader strategies to optimize overall health.
“For most lung diseases, the majority of the literature on gut health that changes lung disease pathogenesis is from research studies,” explained Rachel Scheraga, MD, pulmonologist and critical care physician at Cleveland Clinic in Cleveland. Although studies have explored gut metabolites and lung microbiome changes associated with gut dysbiosis, they cannot yet lead to evidence-based dietary interventions for patients without further clinical trials in humans.
But there are some practical gut-lung connection that currently impact practice. For instance, when gut dysfunction is suspected, pulmonologists at Cleveland Clinic refer patients to gastroenterology to rule out other contributing conditions such as reflux. This is an especially important step in patients with end-stage lung disease awaiting transplant, given the link between poor gut health and an increased risk for transplant rejection.
“The main gap is for the pulmonologist to determine what context the gut may be contributing to either the acute or chronic disease and the proper time to screen for gut dysfunction,” Scheraga said. “I believe it is important to start with translational research to determine the cause and effect of the contribution of gut dysfunction to lung disease. Once it is determined what specifically the gut is doing to cause lung disease progression, then clinical research can be performed to modify this factor and see if the lung disease improves.”
Mechanistic Insights: Linking Gut Microbes to Lung Outcomes
At the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, George A. O’Toole, PhD, is exploring the association between the gut microbiome and CF.
“Linking the gut to the lung is a complex process that requires a team of researchers in the clinic and at the bench,” he shared. “Bench scientists need to understand the clinical issues, and clinicians can help translate observations from patient care into laboratory studies to better define these connections. This area of research must be collaborative — and pulmonologists play a key role.”
While many studies have documented associations between gut dysbiosis and chronic lung disease, the mechanisms remain poorly defined. O’Toole points to several key questions:
- How are gut microbes influencing the airway?
- Is the effect direct, with microbial metabolites traveling to the lung and modulating immune responses?
- Or are gut microbes shaping immune cells in the gut, which then migrate to the airway?
O’Toole’s work in CF in pediatric populations has validated links between gut pathogens such as Escherichia coli with Pseudomonas aeruginosa airway infections in infants and children. This work has been done in close collaboration with Juliette Madan, MD, MS, and Julie Sanville, DO, physician-scientists at the Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.
“In our CF model, we established the link between gut and airway, and we know this link is driven by propionate,” he said. “I’m excited to understand how propionate tunes the airway response. We are also developing probiotic strategies that I think could have great potential.”
“Understanding this connection lets us develop new means to help address airway disease. We have the opportunity to improve patient outcomes.”
Nutrition: A Modifiable Factor
As diet and nutritional status are recognized as modulators of lung health through the gut-lung axis, personalized nutrition has potential to be as complementary to pharmacologic therapy, said Inês Brandão, PhD, Head of Research at Centro de Apoio Tecnológico Agro Alimentar, Castelo Branco, Portugal, a Portugal-based research and innovation center focused on the agri-food sector.
Adequate protein intake, anti-inflammatory, fiber-rich diets, and the use of probiotics, prebiotics, or symbiotics can help support asthma, COPD, and other respiratory diseases, she said, adding the need for well-designed clinical trials, validated biomarkers, and multidisciplinary care teams.
“Encouraging patients to adopt anti-inflammatory, fiber-rich diets and consider probiotic or prebiotic supplementation may support gut microbiota health and reduce lung inflammation,” she said. “This represents, beyond any doubt, low-risk and cost-effective strategies.”
“Moving forward,” Brandão said, “building a shared understanding through collaboration between researchers, clinicians, and nutrition experts will be essential to provide clear, practical guidance for pulmonologists.”
Brandão, O’Toole, and Scheraga reported having no relevant financial relationships.