Two new studies jointly published in Nature: The Clinical Microbiome reveal that certain species of fungi in the gut play a key role in the development of immune dysregulation and some pediatric allergic diseases — and may be promising targets for new therapies.
One paper by Dr. Stuart Turvey and colleagues based at BC Children's Hospital Research Institute (BCCHR) analyzed data from the CHILD Cohort Study to demonstrate that fungi are informative markers of early-life microbial development and may indicate whether a child may develop diseases such as atopic dermatitis and food allergy at five years of age.
"Hundreds of millions of children worldwide are affected by allergic diseases, and the number is growing," says Dr. Stuart Turvey, senior author on the study, investigator at BCCHR and professor of Pediatrics at the University of British Columbia. "A better understanding of what gives rise to these conditions and how we can prevent them would have an enormous benefit for children around the globe."
Another paper by Dr. Marie-Claire Arrieta and colleagues from the Snyder Institute for Chronic Diseases and the Alberta Children's Hospital Research Institute at the University of Calgary found that infant antibiotic use may have a direct impact on certain yeast species leading to immune dysregulation and allergic asthma.
The two articles together emphasize the importance of the fungal component of the gut microenvironment. The bacterial environment in the gut, known as the microbiome, has been well studied, with recent discoveries in this field having led to several potential new treatments. By comparison, very little research has been done on the fungal inhabitants of the gut — the mycobiome — and their role in disease and immune dysregulation.
The advantage of the two papers being co-submitted is in how they complement each other and reinforce their findings.
Dr. Turvey's paper identifies the association between fungal species and immune dysregulation based on a large cohort study. By analyzing 2,256 samples from 1,409 participants in the first year of life the team found that different fungal species show distinct population trajectories. Among the central players in infant gut fungal development, Saccharomycetaceae increased progressively over the first year, while Malassezia showed the opposite trend.
The team then found that different frequencies of certain fungal species were associated with various immunological diseases. For example, Malassezia was more common in infants who later developed atopic dermatitis.
Dr. Arrieta and her team took a different approach by directly investigating the effect of antibiotics on the mycobiome in a prospective clinical study of young infants less than 6 months of age. Treatment with antibiotics led to an increase in fungal species, particularly that of Malassezia, a group of fungi that is commonly found in the infant gut during early life. In subsequent mouse studies, the team showed that colonization with this fungus led to increased allergic inflammation of immune cells in the gut and the airways.
"These results reveal a previously unrecognized pathway linking early-life antibiotic exposure to allergic disease risk and show how the developing immune system is shaped by fungi within the gut microbiome during a critical window of development," says Dr. Arrieta. "Antibiotics are an essential treatment for young children when needed, but this study shows that there is a previously overlooked effect on the gut mycobiome, allowing species like Malassezia to flourish, and directly impacting immunological function."
These concurrent studies underscore the ecological and immunological significance of Malassezia in early life, positioning the infant mycobiome as a promising target for therapies that could prevent immune dysregulation and pediatric allergic diseases.
