Characteristics Of Intestinal Fungi In Patients With Nonalcoholic Fatty Liver Disease Based On ITS High-Throughput Sequencing

Background: Nonalcoholic fatty liver disease(NAFLD)was strongly related to intestinal bacterial,the intestinal fungi in NAFLD remains to be explored.In this study,we are going to analyze the characteristics of intestinal fungi in NAFLD.Methods: A total of 79 patients with non-alcoholic fatty liver disease who visited to our Hospital from April 2018 to December 2018 were selected,32 of them underwent liver biopsy.A total of 32 healthy subjects matched by gender and age were included as the healthy control group.The ITS2 high-throughput sequencing was used to determine the fungal characteristics in the feces of all subjects,and the differences in fungal composition and diversity between NAFLD patients and healthy controls were compared.Collection of demographic indicators(height,weight,gender and age),as well as the index of liver enzyme(ALT,AST,AKP,GGT)and glucolipid metabolism index(TC,TG,HDL,LDL,FPG and FINS),analysis of the correlation between genus and the above indexes.Finally,through the analysis of relationship between the intestinal fungi and the severity of disease to research its role on the development of NAFLD.Result: This study observed that the diversity of the intestinal fungi from NAFLD patients was higher than that of the control group(p<0.05),besides,the distribution was significantly skewed as the principal component showed that NAFLD was clustered separately from the control group(p<0.001).The proportion of Cladosporium,Talaromyces,Fusarium,Sarcinomyces and Paraphaeosphaeria were much higher in NAFLD,while Saccharomyces,Pyrenochaeta,Pseudopithomyces,Mycoarthris,Lodderomyces,Fusicolla,Herpotrichia,Capronia,Leptosphaeria(all p<0.05)were decreased.Besides,there were significant differences in 6 genus distinguished NASH from non-NASH with an AUC of 0.92(0.82-1.00),while 4genus can be used as predictors of advanced fibrosis with an AUC of 0.92(0.83-1.00).The most notable finding was the Cladosporium genus.Its abundance was significantly increased simultaneously in NASH and advanced fibrosis,distinguished NASH from non-NASH,mild fibrosis from advanced fibrosis with an AUC of 0.77(0.61-0.93)and 0.77(0.57-0.97).Finally,we analyzed the correlations between the intestinal fungi and clinic variables,the abundance of Cladosporium was positively correlated with ALT(rho=0.474,p=0.006),while the abundance of Pulvinula was negatively correlated with both ALT(rho=-0.362,p=0.042)and AST(rho=-0.401,p=0.023),and the abundance of Sarcinomyces was positively correlated with TG(rho=0.568,p=0.001).Conclusions: This study found that a unique fungal microbial flora imbalance existed in NAFLD,which was characterized by changes in biodiversity and composition,and was associated with the severity of NAFLD,suggesting that the intestinal fungi might play an important role in NAFLD.