Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered a worldwide healthcare problem that mirrors the increased prevalence of obesity. Gut microbiota plays a crucial role in the progression and treatment of NAFLD. Bofutsushosan (BTS), a pharmaceutical-grade Japanese traditional medicine, has long been prescribed in Japan for obesity and obesity-related syndrome. Although BTS has been reported to exert an anti-obesity effect in obese patients as well as various obesity-model animals, its effect on gut microbiota is unknown. Here, the effects of BTS on obesity, liver damage, and the gut microbiome in genetically obese mice, ob/ob, were studied. Seven-week-old ob/ob mice were fed a standard diet with (BTS group) or without (CONT group) 5% BTS for 4 weeks. By comparison to the CONT group, the BTS group showed reduced body weight gain and hyperlipidemia as well as improved liver function. Moreover, gut microbiota in the CONT and BTS group formed a significantly different cluster. Specifically, the genera Akkermansia, Bacteroides and an unknown genus of the family Enterobacteriaceae expanded dramatically in the BTS group. Noteworthy, the population of Akkermansia muciniphila, which is reported to elicit an anti-obesity effect and improve various metabolic abnormalities, was markedly increased (93-fold) compared with the CONT group. These results imply that BTS may be a promising agent for treating NAFLD.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a progressive fatty liver injury that excludes other causative disorders in patients who do not abuse alcohol
The body weights at Week 0 in the CONT, BTS, and WILD groups were 40.7 ± 2.2, 40.9 ± 1.5, 22.9 ± 0.6 g, respectively
CONT group showed a marked increase in body weight (26.3% ± 6.4%) over the 4 week study period
Summary
Non-alcoholic fatty liver disease (NAFLD) is a progressive fatty liver injury that excludes other causative disorders in patients who do not abuse alcohol. 25% of NAFLD patients subsequently develop non-alcoholic steatohepatitis (NASH), which increases the risk of developing liver cirrhosis and hepatocellular carcinoma [1,2]. Recent research suggests the gut microbiota is deeply involved in human health and various disease states including obesity and NAFLD [7,8,9,10]. The liver is exposed to microbial metabolites such as short-chain fatty acids and secondary bile acids [13]. Secondary bile acids, which are metabolized from primary bile acid by gut microbiota, have different affinities for the farnesoid X receptor (FXR).
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