key gut microbiota-metabolites associated with severity in metabolic dysfunction-associated fatty liver disease-Metabolic

Abstract: The incidence of metabolic-associated fatty liver disease (MAFLD) is increasing and is an increasingly common cause of cirrhosis and hepatocellular carcinoma. Alterations in gut microbiota have been correlated with the incidence of MAFLD. However, limited information is available regarding the differences in the gut microbiome and metabolomics involved in MAFLD severity. In this study, 70 patients with MAFLD and 22 healthy volunteers were enrolled from Guangdong Province, China. The 16S rRNA gene sequencing and non-targeted metabolomic sequencing were used to evaluate the fecal microbiota and metabolites. The results showed six pivotal genera in the gut microbiota: g_Cloacibacillus, g_Synergistes, g_Pseudoramibacter_Eubacterium, g_Coprococcus, g_Lachnospira, and g_Blautia. In the subgroup analysis, we found that gut microbial diversity increased in the severe MAFLD cohorts. Three genera (g_Parabacteroides, g_Cloacibacillus, and g_Turicibacter) and 91 metabolites were found to be differentially expressed and associated with MAFLD severity. Correlation analysis showed that three gut microbiotas, 14 clinical indices, and 82 differentially expressed metabolites (DEMs) were clustered into an interactive network. Notably, g_Cloacibacillus, which was positively correlated with hepatic function, was linked to four DEMs; g_Turicibacter, which was positively correlated with hepatic function and lipid/glucose metabolism, was related to 13 DEMs. These DMEs were mainly enriched in thiamine metabolism, starch and sucrose metabolism, and the citrate cycle (TCA cycle). This study provides insights into the role of key microbiotas and metabolites in fatty liver disease pathogenesis, especially in the severity of metabolic dysfunction. keywords: Metabolic-associated fatty liver disease; gut microbiota, metabolites; glucose metabolism disorders