Low Short-Chain-Fatty-Acid-Producing Activity of the Gut Microbiota Is Associated with Hypercholesterolemia and Liver Fibrosis in Patients with Metabolic-Associated (Non-Alcoholic) Fatty Liver Disease

Abstract

The aim of this study was to investigate the short-chain fatty acid (SCFA) activity of the gut microbiota of patients with metabolic-associated fatty liver disease (MAFLD). The level and spectrum of short-chain fatty acids (SCFAs) were determined via gas–liquid chromatography. Liver fibrosis was assessed using the FIB-4 index and elastography. Among 42 non-cirrhotic MAFLD patients, 24 had high fecal SCFA levels (group H) and 18 had low fecal SCFA levels (group L). Patients in group H had lower serum uric acid, total cholesterol, and LDL cholesterol levels but a higher BMI than those in group L. All patients in group L and only 37.9% of those in group H were found to have hypercholesterolemia. In patients with hypercholesterolemia, the level of SCFAs was lower than that in patients without hypercholesterolemia. Patients in group H had less liver fibrosis than patients in group L. A total of 50.0% of the patients in group H and 92.3% of those in group L had significant liver fibrosis (≥F2). Patients with significant liver fibrosis had lower levels of fecal SCFAs—particularly acetate and butyrate. The fecal SCFA levels were positively correlated with gamma-glutamyl transferase, total bilirubin levels, BMI, and platelet count and were negatively correlated with FIB-4, liver stiffness, serum total, and LDL cholesterol levels.