Abstract
BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is becoming the most common chronic liver disease. The gut microbiome is regarded to play a crucial role in MAFLD, but the specific changes of gut microbiome, especially fungi, in different stages of MAFLD are not well understood. This study aimed to observe the longitudinal changes of colon bacteria and fungi of mice at different feeding duration of a high-fat and high-fructose diet (HFHFD), and explore the association between the changes and the progression of MAFLD. METHODS: Twenty-eight male C57BL6J mice were randomly assigned to the normal diet (ND) group and HFHFD group. At the 8th and 16th weeks, mice were sacrificed to compare the diversity, composition, and co-abundance network of bacteria and fungi in colon contents among groups. RESULTS: HFHFD-8W mice exhibited increases in Candida and Dorea, and decreases in Oscillospira and Prevotella in comparison to ND-8W mice, HFHFD-16W mice had increases in Bacteroides, Candida, Desulfovibrio, Dorea, Lactobacillus, and Rhodotorula, and decreases in Akkermansia, Aspergillus, Sterigmatomyces, and Vishniacozyma in comparison to ND-16W mice. And compared to HFHFD-8W mice, HFHFD-16W mice had increases in Desulfovibrio, Lactobacillus, Penicillium, and Rhodotorula, and decreases in Talaromyces and Wallemia. Spearman and GEE correlation analysis revealed that Bacteroides, Candida, Desulfovibrio, and Lactobacillus positively correlated with NAFLD activity score (NAS). CONCLUSION: Gut microbiota and mycobiota undergo diverse changes at different stages of MAFLD. CLINICAL TRIAL NUMBER: Not applicable.