Could gut mycobiome play a role in NAFLD pathogenesis? Insights and therapeutic perspectives

The entire spectrum of nonalcoholic fatty liver disease (NAFLD) ranging from fatty liver to cirrhosis has been considered as the result of specific metabolic pathways and mediators, gut barrier function alterations and inflammatory responses. Previous studies have associated intestinal microbiota with NAFLD pathogenesis, focusing mostly on bacteria. In a recent study by Demir et al. in the Journal of Hepatology, researchers characterized the fecal mycobiome of patients with NAFLD and controls. NAFLD severity was linked to a specific fecal mycobiome signature, particularly in patients without obesity, highlighting previously undescribed aspects of the non obese phenotype of NAFLD. There has recently been a growing interest in the pathophysiology and progression of non obese NAFLD, as its actual incidence seems to be higher than previously described. Moreover, the authors demonstrated that in subjects with NAFLD and advanced fibrosis, there was an augmented systemic immune response to Candida albicans. Amphotericin B, which has been widely regarded as an antifungal with a good safety profile, low rate of resistance and high efficacy, has already been shown to prevent liver injury and steatosis in mice. Similarly in this study when germ-free mice colonized with feces from patients with NASH were fed with a Western diet, treatment with amphotericin B protected against steatohepatitis and liver fibrosis. In conclusion, this study has provided novel insights into the fecal mycobiome composition in advanced NAFLD especially in the non obese population while suggesting a role for antifungal therapy in the management of NAFLD.