The impact of intestinal fungal dysbiosis on zebrafish health and the gut microbiota.

Abstract

The gut mycobiota constitutes a significant component of the intestinal microecosystem in aquatic animals, yet its role in fish health remains elusive. In this study, we systematically investigated the impact of disrupting intestinal fungal homeostasis on host physiological functions and the gut microecosystem using zebrafish (Danio rerio) as a model. Two distinct intestinal fungal perturbation models were established using continuous and intermittent antifungal treatments. The results demonstrated that fungal dysbiosis impaired growth, suppressed the expression of core growth-axis and nutrient absorption-related genes, disrupted hepatic metabolic homeostasis, weakened antioxidant capacity, and damaged the intestinal barrier. Furthermore, fungal dysbiosis disrupted immune balance, as characterized by upregulated pro-inflammatory factors, downregulated anti-inflammatory mediators, and suppressed repair signals. Concurrently with the remodeling of the fungal community (e.g., a shift in dominance from Ascomycota to Cryptomycota), the bacterial community exhibited a decrease in the probiotic genus Cetobacterium and a significant increase in the opportunistic pathogen Aeromonas. This study demonstrates that intestinal fungi in fish are critical regulators of host metabolism, immunity, and microecosystem homeostasis, beyond being mere nutritional symbionts. It also highlights the potential disruption of microbial interaction networks by antifungal agents. Collectively, this research enhances our understanding of fungal functions in aquatic organisms and provides a crucial scientific foundation for developing sustainable aquaculture strategies based on fungal modulation.