Mycobiome matters? Rethinking the role of fungi in depression and anxiety: a hypothesis-driven perspective

This literature review explores how fungi, mycotoxins and yeast-based interventions may influence depressive disorders through the gut-brain axis. Although depression remains a highly prevalent and multifactorial condition, growing evidence shows that the intestinal microbiota plays an important role in its development and in shaping responses to treatment. Most of what is known today comes from studies focused on bacterial communities, which consistently reveal patterns of dysbiosis in individuals with Major Depression Disorder. However, recent findings suggest that the fungal component of the gut microbiota may also shift in depressive states, with alterations in species such as Candida , Penicillium , Saccharomyces and others, emerging across human and animal studies. From a pathological perspective, mycotoxins, particularly fumonisin B1, have also been implicated in the development of depressive-like symptoms in murine models. Beyond characterizing these associations, this review highlights experimental work demonstrating that fecal microbiota transplant from depressed individuals to germ-free rodents can reproduce metabolic and behavioral features of the disorder, reinforcing the relevance of the microbiota-gut-brain axis. In parallel, the review examines evidence on probiotic and postbiotic yeasts, from live Saccharomyces to heat-inactivated yeast cells and their structural components, which show potential to modulate inflammation, restore intestinal integrity, and alleviate stress-related behaviors. Together, these insights frame fungi and yeast-derived products as promising, yet underexplored, candidates for future therapeutic strategies targeting depression.