The combination of berberine, tocotrienols and coffee extracts improves metabolic profile and liver steatosis by the modulation of gut microbiota and hepatic mir‐122 and mir‐34a expression in mice

Non‐alcoholic‐fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin‐resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR‐122 and miR‐34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E‐mice showed lower body weight (p < 0.01), amelioration of insulin‐sensitivity (p = 0.021), total cholesterol (p = 0.014), low‐density‐lipoprotein‐cholesterol (p < 0.001), alanineaminotransferase (p = 0.038) and hepatic steatosis compared to HFD‐mice. While a decrease of hepatic miR‐122 and increase of miR‐34a were observed in HFD‐mice compared to SD‐mice, both these miRNAs had similar levels to SD‐mice in HFD+E‐mice. Moreover, a different microbial composition was found between SD‐ and HFD‐mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD‐induced NAFLD by the modulation of miR‐122, miR‐34a and gut microbiome.