Association Of Short-chain Fatty Acids-producing Bacterial Diet And Fatty Liver Disease:A Cross-sectional Study

ObjectiveThe prevalence of fatty liver disease in China is increasing,and it has become the second largest liver disease after viral hepatitis.Previous studies have suggested that high fiber diet and its metabolite short-chain fatty acids（SCFAs）can reduce the risk of fatty liver disease,and dietary fiber must rely on specific intestinal flora to metabolize SCFAs;on the other hand,diet can affect the structure and function of intestinal flora.Therefore,we hypothesized that diet may affect the risk of fatty liver disease in part by affecting the production of specific gut microbiota and their metabolites SCFAs.In order to verify the above hypothesis,this study constructed a dietary pattern that can reflect the abundance of SCFAs-producing bacteria in vivo,namely SCFAs-producing bacterial diet（SPBD）,and verified the ability of this dietary pattern to predict the relative abundance of SCFAs-producing bacteria.At the same time,the association between SPBD compliance and fatty liver disease was analyzed in a community-based cross-sectional study.MethodsA community-based cross-sectional study was conducted in Huoshan County,Lu’an City,Anhui Province.Multistage sampling method was used to select subjects aged 18 and over.The dietary information was obtained through the food frequency questionnaire,and the demographic characteristics and body measurement data of the subjects were collected.Stool samples were subjected to 16S r RNA gene sequencing,and blood samples were tested for blood lipids and liver function.The subjects who could provide qualified fecal specimens were randomly divided into building set（n=270）and validation set（n=122）at a ratio of 2:1.In the training set,the relative abundance of 10 intestinal flora related to the production of SCFAs（propionic acid and butyric acid）was used as the response variable,and 41 food groups were used as predictors.SPBD was constructed by reduced rank regression and stepwise linear regression.The higher the individual SPBD score,the stronger the compliance with the dietary pattern.In the validation set,multivariate linear regression analysis was used to analyze the ability of SPBD compliance score to predict the abundance of 10 SCFAs-producing bacteria.The association between SPBD compliance score and fatty liver disease was analyzed in the total population（n=392）.Fatty liver index（FLI）was used to evaluate the prevalence of fatty liver disease.Multivariate logistic regression analysis was used to analyze the odds ratio（OR）and 95%confidence interval（CI）of SPBD compliance score and fatty liver disease（FLI³30）.Multiple linear regression analysis was used to analyze the correlation between SPBD and serum liver function indexes,and the percentage change was calculated by regression coefficient.The association between food groups and fatty liver disease in SPBD was also analyzed.ResultsThe constructed SPBD included 15 food groups,in which the relative abundance of bacteria and algae,bean products,tea,other vegetables,bean drinks,and other aquatic products was positively correlated with the relative abundance of SCFAs-producing bacteria.Salted vegetables,red meat,animal viscera,shrimps,eggs,spirits,condiments,grilled foods and sugary beverages were negatively correlated with the relative abundance of SCFAs-producing bacteria.In the validation set,after adjusting for potential confounding factors,the percentage changes（95%CI）of the relative abundance of SCFAs-related bacteria in the lowest to highest tertiles of SPBD compliance scores were20.1%（95%CI:-15.6%～71.0%）and 96.9%（95%CI:39.1%～178.7%）,respectively,and the linear trend was statistically significant(P_trend<0.001),suggesting that SPBD compliance scores can better predict the abundance of SCFAs-related bacteria.After adjusting for confounding factors,compared with the lowest tertile of SPBD compliance score,the highest tertile had a lower prevalence of fatty liver disease(OR=0.44,95%CI:0.24-0.79,P_trend=0.006).The SPBD score was negatively correlated with the level of glutamyl transferase（GGT）.Compared with the first quartile,the percentage change of GGT level in the second and third quartiles was-9.78%（95%CI:-21.49%～3.67%）,-15.70%（95%CI:-26.54%～-3.27%）,and the linear trend was statistically significant(P_trend=0.015).There was no significant correlation between alanine aminotransferase(P_trend=0.375)and aspartate aminotransferase(P_trend=0.975).Among the 15 SPBD food components,the intake of pickles（OR=1.27,95%CI:1.00-1.61）,condiments（OR=1.34,95%CI:1.02-1.75）and barbecue food（OR=1.54,95%CI:1.11-2.14）was significantly positively correlated with fatty liver disease.No statistical association was observed between other food groups and fatty liver disease.ConclusionIn this study,a dietary pattern SPBD related to SCFAs production was constructed for the first time in the community population,which can better predict the relative abundance of intestinal flora related to individual SCFAs production.The SPBD score was negatively correlated with the prevalence of fatty liver disease and serum GGT levels.The results suggest that the effect of diet on liver steatosis can be partially mediated by the intermediate mechanism of intestinal flora and its dependent metabolite SCFAs,which has certain mechanism significance.Following the SPBD diet pattern is associated with a reduced risk of fatty liver disease,which has certain public health significance.