IIS La Fe and FISABIO study identifies fungal microbiota alterations in patients with common variable immunodeficiency

The research reveals that these patients exhibit lower fungal diversity and a higher abundance of opportunistic species, such as Candida albicans, in saliva, sputum and stool samples.

Furthermore, fungal profiles were able to distinguish patients from healthy controls with high accuracy, particularly in saliva. These findings pave the way for the future development of non-invasive biomarkers to improve the understanding, stratification and monitoring of common variable immunodeficiency.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency and is characterised by marked clinical heterogeneity. Patients may experience recurrent infections as well as inflammatory, autoimmune, gastrointestinal or pulmonary complications. Despite advances in understanding the disease, important questions remain regarding the mechanisms underlying this wide range of clinical manifestations.

Reduced diversity and increased opportunistic fungi

The study, entitled Multiniche Mycobiome Profiling Identifies Distinctive Fungal Dysbiosis in Common Variable Immunodeficiency, provides the first integrated characterisation of the mycobiome across multiple mucosal niches in this immunodeficiency. To achieve this, the researchers analysed samples from 41 adults with common variable immunodeficiency-24 with immune dysregulation-associated disease and 17 with predominantly infectious manifestations-as well as 15 matched healthy controls, using ITS1 sequencing together with a range of bioinformatics and statistical analyses.

As in any ecosystem, maintaining a balance between species is essential in the human body. Until now, research into common variable immunodeficiency has focused primarily on the bacterial microbiota, while the role of fungi has received much less attention. This study demonstrates that the composition of the mycobiome differs significantly between patients with common variable immunodeficiency and healthy individuals across all three mucosal niches analysed: the oral cavity, the respiratory tract and the gut.

The results show reduced fungal richness and evenness in patients with common variable immunodeficiency, particularly in oral and respiratory samples, indicating a loss of diversity within these microbial communities. The study also identified a recurrent fungal configuration dominated by Candida, with a marked increase in Candida albicans in saliva, sputum and stool samples, accompanied by other opportunistic yeasts such as Nakaseomyces glabratus. Conversely, the abundance of other fungal species that would normally coexist harmlessly within this ecosystem was reduced.

This finding is particularly relevant because it suggests that dysbiosis in common variable immunodeficiency affects not only bacteria but also fungi, a component of the microbiota that has traditionally been far less studied. According to the authors, the expansion of Candida albicans supports its potential role as a pathobiont-that is, a microorganism that normally coexists harmlessly with the host but may contribute to microbial imbalance under conditions of immune dysfunction.

Towards Future Non-Invasive Biomarkers

In addition to characterising these alterations, the study assessed whether fungal profiles could be used to distinguish patients with common variable immunodeficiency from healthy individuals. Machine learning-based models demonstrated a high discriminatory performance, achieving an area under the curve (AUC) of up to 0.96 for saliva samples and 0.94 for stool samples. However, their ability to differentiate between clinical subtypes of the disease was more modest.

These findings suggest that mycobiome signatures in accessible, non-invasive samples such as saliva and stool could, in the future, be explored as complementary biomarkers for the identification and monitoring of patients with common variable immunodeficiency. Nevertheless, the authors emphasise that these results must be validated in larger cohorts before they can be translated into clinical practice.

A New Avenue for Understanding the Disease

Beyond its potential clinical applications, the study advances scientific knowledge of common variable immunodeficiency by incorporating the mycobiome into the map of microbial alterations associated with this condition. The findings generate new hypotheses regarding the interactions between the immune system, mucosal surfaces and microorganisms, and may help explain why the same disease can give rise to such diverse clinical manifestations among patients.

This research is of interest not only to people living with common variable immunodeficiency and other primary immunodeficiencies, but also to specialists in immunology, internal medicine, infectious diseases and microbiology, as well as to the wider scientific community investigating the relationship between the microbiota, immunity and inflammation.

The study also highlights the importance of investigating the fungal component of the microbiota, which has often been overshadowed by bacterial research despite its potentially crucial role in health and disease.

Cabanero-Navalon, M. D., Carda-Diéguez, M., Mira, A., Moral Moral, P., Diaz Luna, M. M., Balastegui-Martín, H., Salavert Lletí, M., & Garcia-Bustos, V. (2026). Multiniche mycobiome profiling identifies distinctive fungal dysbiosis in common variable immunodeficiency. Frontiers in Immunology, 17, Article 1804724. https://doi.org/10.3389/fimmu.2026.1804724