| Objective: Nonalcoholic fatty liver disease(NAFLD)is a metabolic stress liver injury closely associated with insulin resistance(IR)and genetic susceptibility.The spectrum of diseases includes Nonalcoholic simple hepatic steatosis(NAFL),Nonalcoholic steatotic hepatitis(NASH),Cirrhosis,and Hepatocellular carcinoma(HCC).With the increasing prevalence of obesity and other metabolic syndromes,NAFLD has become the most common chronic liver disease in the world.It is currently believed to be the result of "multiple strikes",including genetic factors,dietary factors,insulin resistance(IR),endocrine abnormalities,chronic oxidative stress,and gut microbiota disorders.In recent years,In recent years,with the deeper understanding of intestinal flora,many studies have shown that intestinal flora disorder plays an important role in the occurrence and development of NAFLD.However,few reports have been published on how intestinal flora affects liver function through metabolic pathways.In this study,clinical biochemical indexes,fecal intestinal flora and fecal Short-chain fatty acid(SCFA)levels of patients with different degrees of NAFLD were determined to explore the possible mechanism of intestinal flora’s involvement in the occurrence and development of NAFLD.Methods: Sixty-six patients with NAFLD were recruited to form the NAFLD group,then it was further divided into mild,moderate and severe according to the b-mode ultrasonic manifestations,including 40 patients with mild,22 patients with moderate and 4 patients with severe.During the same period,18 healthy patients were randomly selected as the healthy control group.All subjects were measured in basic indicators such as height,weight,waist circumference,hip circumference,etc.,and 5ml fasting venous blood in the morning was collected,using automatic biochemical analyzer to detecte the serum biochemical indicators.Fecal samples from four groups were collected,and using 16 S r RNA sequencing technology to detecte fecal intestinal flora.OTU cluster and species taxonomic analysis were conducted after the samples were distinguished by comparing and optimizing sequences.The above fecal samples were further analyzed by gas chromatography for the metabolites of intestinal flora,which focus on levels of SCFA,to explore the potential association of gut microbiota and SCFA in patients with NAFLD.Results: 1.Clinical biochemical indicators: BMI,waist circumference,hip circumference,ALT,GGT,TC and FPG in the NAFLD group were higher than those of healthy control group,while ALB,HDL,LDL and IBIL were lower than those of healthy control group.In the NAFLD group,BMI,waist circumference,hip circumference,AST,ALT of moderate patients and BMI,hip circumference of severe patients were higher than that of mild patients,AST,ALT and GGT in severe patients were higher than those in mild and moderate patients,with statistically significant differences(P<0.05).In addition,there was a significant correlation between the severity of NAFLD under b-mode ultrasound and the biochemical indexes.2.At the level of phylum,the proportion of bacteroidetes in the intestinal flora of NAFLD patients was lower than that of the control group,and the proportion of firmicutes was higher than that of the control group.On the genus level,the proportion of Unclassified Enterobacteriaceae,Megamonas,Megasphaera,Ruminococcus,Haemophilus in NAFLD is higher than healthy controls.In the NAFLD group,Unclassified-Lachnospiraceae is richer than healthy controls and mild patients,Parasutterella is lower than healthy controls in moderately and severe patients,Fusobacterium in moderate patients is higher than mild patients,and the differences were statistically significant(P<0.05).In addition,there was a significant correlation between different gut microbiota and clinical biochemical indicators.3.The levels of fecal short-chain fatty acids in NAFLD and the healthy control group were detected by gas chromatography,and the contents of acetic acid and total SCFA in the NAFLD group were significantly lower than those in the healthy control group,and the contents of iso-valerate were significantly higher than those in the healthy control group.The level of acetic acid in the moderate NAFLD group was significantly lower than that of healthy control,with statistically significant differences(P<0.05).In addition,there was a significant correlation between different intestinal flora and SCFA.Conclusions: Patients with NAFLD have abnormal biochemical indexes and gut microbiota disorders.Differential bacteria may influence the process of NAFLD by affecting liver function and changing the metabolic state of Short-chain fatty acids. |
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