A role for gut mycobiome and altered fungal-bacterial interactions in women with endometriosis†.

Endometriosis is a gynecological pathology prevalent in reproductive age women in which the inner uterine wall (endometrium) grows outside as ectopic lesions. The inflammation resulting from these growing implants closely associates with disease severity, causing chronic pain and infertility. Emerging studies have found altered bacterial communities in endometriosis and a causal role for gut bacteria in endometriosis. However, the role of the gut mycobiome, i.e., the fungal component of the microbiome in endometriosis is a current knowledge gap that needs to be addressed. In this study, utilizing the stool samples from women with endometriosis, we found that the gut fungal communities are altered in women with endometriosis. By integrating the bacterial microbiota and studying the co-occurring relationships between fungi and bacteria, we identify the altered fungal-bacterial community interactions in endometriosis. In addition, we studied the microbial interactions with the host and identified the bacterial taxa as "microbiome-associated host genetic variants" in endometriosis. By determining their interactions with fungi, we highlight the fungal taxa as underlying regulators of the disease. Experimentally, we demonstrate that the progression of endometriosis in mice is significantly impeded by the depletion of fungi, revealing a role for the gut mycobiome in endometriosis. Our results highlight the positive- and negative-co-abundance relationships shared between bacteria-fungi, bacteria-bacteria, and microbes-host in the disease pathogenesis. These findings could help shape future experimental research on bacterial-fungal interactions, which should be considered when designing microbiome-based therapies that use antifungal agents.