The human body is in constant interaction with a complex group of micro-organisms like bacteria, viruses and fungi which populate various body surfaces like our skin, lungs and gut. These organisms generally do not pose a threat to the host but in contrary have many beneficial functions like stimulating the correct development of our immune system. Until now, research has mainly focused on bacteria, while fungi have largely been overlooked. Enteric fungi represent a significant part of the intestinal microbiota, but their role in human health and disease is barely studied. Spondyloarthritis (SpA) is a common immune pathology that causes severe spine and joint inflammation. The lab of Prof. Dirk Elewaut was the first to show a mechanistic link between spondyloarthritis and intestinal inflammation. Interestingly, anti-fungal immune responses require Th17 immune activation, an immune arm commonly hyperactivated in arthritic disease. We, therefore, hypothesize that aberrant antifungal immune responses may be contributing to arthritic pathology. Alternatively, homeostatic fungal-host interactions may be important for both mucosal and systemic immune homeostasis. With the FungArth project, I studied in detail the contribution of naturally occurring intestinal fungi to health and SpA development in a multi-disciplinary manner, using elegant genetic mouse models of disease, state-of-the-art technologies and clinical samples from SpA patients.
The Marie-Curie fellowship is now ended but I am continuing the project in the lab, finishing some experiments and testing new hypotheses. Here are the main findings and the continuation of the project:
I evidenced a role of fungal communities in the SpA disease development. Indeed, antimycotic treatment induced a higher clinical scoring all along the duration of the treatment in mouse models. These results are confirmed at the joint level, where the inflammation is worsened with the antimycotic treatment. While antibiotic treatments have a protective effect in gut inflammation, no effect on arthritis has been observed.
These results suggest a protective effect of fungi, potentially slowing down disease development. The antimycotic treatment targeted specific yeast species, those yeast are currently inoculated in germfree mice and conventional disease models in order to confirm the hypothesis.
I also worked with samples from SpA patients (biopsies and feces): extracting both DNA and RNA in order to profile bacterial and fungal communities but also evaluate the gene expression. The biopsies extractions and sequencing are achieved (385 samples in total) and I am currently analyzing the results.
