Ginsenoside Rc ameliorated atherosclerosis via regulating gut microbiota and fecal metabolites

Abstract

Atherosclerosis (AS) and the accompanied cardiovascular diseases (CVDs) were the leading cause of death worldwide. Recently, the association between CVDs, gut microbiota, and metabolites had aroused increasing attention. In the study, we headed our investigation into the underlying mechanism of ginsenoside Rc (GRc), an active ingredient of ginsenosides used for the treatment of CVDs, in apolipoprotein E-deficient (ApoE −/− ) mice with high-fat diet (HFD). Sevenweek-old male ApoE −/− mice were randomly divided into four groups: the normal control (NC) group, the HFD group, the GRc group (40 mg/kg/d), and the atorvastatin (Ato) group (10 mg/kg/d). Atherosclerotic injury was evaluated by aortic lesions, serum lipid levels, and inflammatory factors. The composition of gut microbiota and fecal metabolite profile were analyzed using 16S rRNA sequence and untargeted metabolomics, respectively. The results showed that GRc significantly alleviated HFD-induced aortic lesions, reduced serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 and IL-1β, and increased high-density lipoprotein cholesterol (HFD-C) level, as well as the alteration of gut microbiota composition, function, and metabolite profile. GRc also reversed HFD change of Bacteroidetes and Firmicutes at the phylum level, Muribaculaceae, Lactobacillus, Ileibacterium, Bifidobacterium, Faecalibaculum, Oscillibacter, Blautia, and Eubacterium_coprostanoligenes_group at the genus level, and 23 key metabolites involved in taurine and hypotaurine metabolism, arginine biosynthesis, ATP-binding cassette (ABC) transporters, primary bile acid biosynthesis, purine metabolism, tricarboxylic acid (TCA) cycle, and glucagon signaling pathways. Additionally, eight differential intestinal floras at the genus level were associated with 23 key differential metabolites involving atherosclerotic injury. In conclusion, our results demonstrated that GRc ameliorated atherosclerotic injury, regulated microbial and metabolomic changes in HFD-induced ApoE −/− mice, and suggested a potential correlation among gut microbiota, metabolites, and atherosclerotic injury regarding the mechanisms of GRc against AS.

Lactobacillus acidophilus CICC 6075 Attenuates HFD-induced Obesity by Improving Gut Microbiota Composition and Histidine Biosynthesis

“…Additionally, HFD-induced obesity reduces Ileibacterium spp., and the abundance of these bacteria is negatively correlated with chronic in ammatory diseases such as obesity, atherosclerosis, and aging [40][41][42]. It has been reported that Helicobacter negatively correlates with intestinal tight junction protein expression, which increases after HFD feeding [43].…”

Differences in the intestinal microbiota and association of host metabolism with hair coat status in cattle

“…Our study identified the biomarkers of intestinal microbiota, which included included g__norank_f__Eubacterium_coprostanoligenes_group as a potential predictor for hair coat status. The effects of this genus may involve the reduction of cholesterol ( Freier et al, 1994 ), lipid and bile acid metabolism ( Xie et al, 2022 ), maintenance of colonic mucus barrier function, and decreased systemic inflammation ( Bai et al, 2021 ; Yang et al, 2021 ). Interestingly, this beneficial genus has also been reported to be enriched in fecal samples from high-productivity sows, compared to their low-productivity counterparts during late pregnancy ( Shao et al, 2019 ), as well as in the rumen of high-yield cows receiving the same diet ( Tong et al, 2018 ).…”

Meta-analysis of the effect of probiotics or synbiotics on the risk factors in patients with coronary artery disease

“…Gut microbes have the ability to positively modulate the host immune system, play an immunomodulatory role, defend against pathogenic microbes, and maintain normal physiological functions (20). Studies have indicated that treatment targeting gut microbes can delay the progression of coronary lesions (21). Although there have been meta-analyses on the effects of probiotics on lipid metabolism, glucose metabolism, blood pressure, and inflammatory factors (22,23), they do not consider the effects of conventional drugs on the intestinal flora (24)(25)(26).…”