Abstract
Structural disruption of gut microbiota is closely related to the occurrence of non-alcoholic fatty liver disease (NAFLD). Previous research has demonstrated that both curcumin (CUR) and metformin (MET) have a therapeutic effect against NAFLD and play a role in modulating the gut microbiota. However, there is a lack of direct comparison between the two medications in terms of the therapeutic efficacy and the regulatory effect on gut microbiota. In this study, we administered either CUR or MET to rats with high-fat diet (HFD)-induced obesity to observe changes in body parameters, biochemical parameters, liver, and ileum pathology and gut microbiota, and used next generation sequencing and multivariate analysis to evaluate the structural changes of gut microbiota in a NAFLD rat model before and after CUR and MET intervention. It was found that both CUR and MET attenuated hepatic ectopic fat deposition, alleviated inflammatory factors, and improved intestinal barrier integrity in HFD-fed rats. More importantly, CUR and MET reduced the Firmicutes/Bacteroidetes ratio and reverted the composition of the HFD-disrupted gut microbiota. Both CUR and MET treatments effectively modified the gut microbiome, enriched the abundance of beneficial bacteria and reduced opportunistic pathogens in obese rats. The abundance of Butyricicoccus was increased while the abundance of Dorea was decreased in HFD + CUR group. Besides, some beneficial bacteria such as Prevotella were increased in MET-treated animals. Spearman’s correlation analysis showed that Helicobacter, Akkermansia, Desulfovibrio, Romboutsia, Corynebacterium, Lactobacillus, Ruminococcaceae_unclassified, Lachnospiraceae_unclassified, and Clostridiales_unclassified showed significantly positive correlations with TG, TC, LDL-C, GLU, IL-6, IL-1β, and TNF-α, and negative correlations with HDL-C (both p < 0.05). However, Prevotella and Stomatobaculum showed an opposite trend. In summary, CUR and MET showed similar effects in alleviating hepatic steatosis, improving intestinal barrier integrity and modulating gut microbiota in HFD-induced obesity rats, and therefore may prove to be a novel adjunctive therapy for NAFLD.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, with a prevalence varying from 25 to 40% worldwide (Younossi et al, 2016)
NAFLD is a clinical pathological syndrome ranging from non-alcoholic simple fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and hepatocellular carcinoma (HCC) (Abdul-Hai et al, 2015)
Another study provided new evidence that CUR supplementation significantly shifted the ratio between beneficial and pathogenic microbiota (Feng et al, 2017). These findings suggest that CUR has the potential to cure dyslipidemia and NAFLD
Summary
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, with a prevalence varying from 25 to 40% worldwide (Younossi et al, 2016). New evidence has shown that change in the gut microbiota composition can influence nutrient acquisition and energy regulation of the host, which could result in IR and diabetes (Ma et al, 2017). This indicates that the gut microbiota plays a key role in the development and progression of NAFLD, and modulating the gut microbiota may be a novel strategy for NAFLD prevention. Another study provided new evidence that CUR supplementation significantly shifted the ratio between beneficial and pathogenic microbiota (Feng et al, 2017) These findings suggest that CUR has the potential to cure dyslipidemia and NAFLD. The efficacy of CUR on fatty liver disease remains largely unknown
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