A research team has uncovered a new communication pathway linking the gut and lungs. Their discoveries reveal how a lesser-known gut microbiome component alters the lung’s immune environment, yielding both positive and negative impacts on respiratory health.
Researchers at the University of Toronto have identified a novel communication channel between the gut and the lungs.
These findings demonstrate how a relatively obscure microbiome inhabitant modifies the lung’s immune environment, influencing respiratory health in both beneficial and harmful ways.
“The harmonious gut microbes that reside in our intestines play a crucial role in regulating our immune system. Increasing evidence links these commensal microorganisms to various conditions affecting other organs, including the lungs, brain, skin, or joints,” explains Arthur Mortha, an associate professor of immunology at the Temerty Faculty of Medicine at U of T.
In recent decades, shifts in the gut microbial makeup have been associated with various traits and health issues, including obesity, allergies, cancer, and mental health problems. However, most of these studies have predominantly targeted bacteria, the most abundant microbes in the gut.
The latest study, published in the journal Cell, shifts the focus to protozoa, a different group of microorganisms. While protozoa are also single-celled like bacteria, they are much larger and have more complex structures. Although most known protozoa are considered parasites, some lesser-known species can live beneficially alongside their animal hosts.
Mortha states, “Our goal was to explore how commensal protozoan species in the gut influence disease outcomes and our overall health.” He also holds the Canada Research Chair in Mucosal Immunology.
The study was led by Kyle Burrows, a postdoctoral fellow in Mortha’s lab who will assume a position as an assistant professor at Simon Fraser University in early 2025.
The researchers investigated a protozoan known as Tritrichomonas musculis, or T. mu, which harmlessly inhabits the guts of mice.
They discovered that mice carrying T. mu exhibited unusually high levels of specific immune cells in their lungs. Notably, some of these immune cells originated in the gut and traveled to the lungs, where they adjusted the local immune environment, influencing outcomes related to respiratory diseases and infections.
According to Mortha, “By promoting the production and movement of these immune cells from the gut to the lung, T. mu acts as ‘a conductor in the intestine that orchestrates the immune system to distribute to other body regions.’”
A major takeaway from the study was that the immune changes prompted by T. mu in the lung aggravated airway inflammation associated with allergic asthma but seemed to provide a protective effect against respiratory infections.
In collaboration with molecular genetics professor Jun Liu, the researchers utilized the Toronto High Containment Facility to examine how the modified immune landscape affects tuberculosis. They found that increased levels of immune cells in the lungs of mice colonized by T. mu acted as an antimicrobial barrier in the airways, aiding in controlling tuberculosis infections and slowing their spread to other organs.
Mortha observes that these findings align with prior observations made by his team regarding the contradictory effects of T. mu on various aspects of gut health in mice. “This protozoan significantly impacts the immune system in the intestinal tract,” he states. “It worsens colorectal cancer and inflammatory bowel disease but simultaneously equips the host to counter severe infections.”
Additionally, the researchers examined sputum samples from individuals with severe asthma. They looked for genetic markers associated with human protozoa and found increased signals in samples from severe asthma patients compared to those with non-asthmatic inflammatory lung conditions, suggesting that the results seen in mice may also apply to humans.
Mortha believes these discoveries could lead to novel diagnostic and therapeutic strategies for asthma and potentially other chronic inflammatory diseases.
For instance, identifying specific protozoa might help predict which patients are at risk of developing severe asthma and help tailor medications based on the immune pathways engaged by the protozoa.
“Can we prevent or slow asthma development with treatments that focus not only on the lungs but also target the intestinal tract?” he wonders.
Moving forward, the researchers are also exploring other organs that might be influenced by the gut microbiome and are tracking the journey of immune cells from the gut to these organs.
Mortha concludes, “This movement of immune cells between organs showcases a new communication method among them, particularly through gut microbes.”
“It transforms our understanding of the relationship with our microbiome and emphasizes the need to consider not just bacteria but also protozoa and other overlooked microbes to enhance our insights into health and disease.”
