Curcumin supplementation alleviates hepatic fat content associated with modulation of gut microbiota-dependent bile acid metabolism in patients with non-alcoholic simple fatty liver disease: a randomized controlled trial

Our previous studies showed that curcumin prevented hepatic steatosis in animal models. This study aimed to assess the effects of curcumin on hepatic fat content, body composition, and gut microbiota-dependent bile acid (BA) metabolism in patients with non-alcoholic simple fatty liver (NASFL). In a 24-week double-blind randomized trial, 80 patients with NASFL received 500 mg/d curcumin or placebo. Hepatic fat content was measured using FibroTouch-based controlled attenuation parameters (CAP). Microbial composition and BA metabolites were analyzed using 16S rRNA sequencing and metabolomics. Curcumin consumption significantly reduced CAP value compared to placebo (-17.5 dB/m; 95%CI: -27.1, -7.8; P < 0.001). This corresponded to reduction in weight (-2.6 kg; 95%CI: -4.4, -0.8; P < 0.001) and BMI (-1.0 kg/m2; 95%CI: -2.0, -0.1; P = 0.032) compared to placebo group. Additionally, free fatty acid (-0.12 mmol/L; 95%CI: -0.20, -0.04; P = 0.004), triglycerides (-0.29 mmol/L; 95%CI: -0.41, -0.14; P < 0.001), fasting blood glucose (-0.06 mmol/L; 95%CI: -0.12, -0.01; P = 0.038), HbA1c (-0.06%; 95%CI: -0.33, -0.01; P = 0.019), and insulin (-4.94 μU/L; 95%CI: -9.73, -0.15; P = 0.043) showed significant reductions in the curcumin group compared to placebo group. Gut microbiota analysis indicated that curcumin significantly decreased Firmicutes to Bacteroidetes ratio and significantly increased Bacteroides abundance. Serum levels of deoxycholic acid, the most potent activator of Takeda G protein-coupled receptor 5 (TGR5), were significantly elevated after curcumin intervention (37.5 ng/mL; 95%CI: 6.7, 68.4; P = 0.018). Curcumin treatment also increased TGR5 expression in peripheral blood mononuclear cells and serum glucagon-like peptide-1levels (0.73 ng/mL; 95%CI: 0.16, 1.30; P = 0.012). Improvements in gut microbiota-dependent BA metabolism and TGR5 activation after 24-week curcumin intervention were associated with a reduction in hepatic fat content in patients with NASFL, providing evidence that curcumin is a potential nutritional therapy for NASFL. The trial was registered at www.chictr.org.cn https://www.chictr.org.cn/showproj.html?proj=155570 ChiCTR2200058052