Dataset Information

Phytosterols Alleviate Hyperlipidemia by Regulating Gut Microbiota and Cholesterol Metabolism in Mice.

ABSTRACT: Phytosterols (PS) have been shown to regulate cholesterol metabolism and alleviate hyperlipidemia (HLP), but the mechanism is still unclear. In this study, we investigated the mechanism by which PS regulates cholesterol metabolism in high-fat diet (HFD) mice. The results showed that PS treatment reduced the accumulation of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the serum of HFD mice, while increasing the serum levels of high-density lipoprotein cholesterol (HDL-C). Compared with HFD mice, PS not only increased the antioxidant activity of the liver but also regulated the mRNA expression levels of enzymes and receptors related to cholesterol metabolism. The hypolipidemic effect of PS was abolished by antibiotic (Abx) intervention and reproduced by fecal transplantation (FMT) intervention. The results of 16S rRNA sequencing analysis showed that PS modulated the gut microbiota of mice. PS reduced the relative abundance of Lactobacillus and other bile salt hydrolase- (BSH-) producing gut microbiota in HFD mice, which are potentially related to cholesterol metabolism. These findings partially explain the mechanisms by which PS regulates cholesterol metabolism. This implies that regulation of the gut microbiota would be a potential target for the treatment of HLP.

SUBMITTER: Lv WJ

PROVIDER: S-EPMC10156461 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Phytosterols Alleviate Hyperlipidemia by Regulating Gut Microbiota and Cholesterol Metabolism in Mice.

Lv Wei-Jie WJ Huang Jie-Yi JY Lin Jin J Ma Yi-Mu YM He Shi-Qi SQ Zhang Ying-Wen YW Wang Tian-Ze TZ Cheng Ke K Xiong Ying Y Sun Feng-Gang FG Pan Zhong-Chao ZC Sun Jing-Bo JB Mao Wei W Guo Shi-Ning SN

Oxidative medicine and cellular longevity 20230426

Phytosterols (PS) have been shown to regulate cholesterol metabolism and alleviate hyperlipidemia (HLP), but the mechanism is still unclear. In this study, we investigated the mechanism by which PS regulates cholesterol metabolism in high-fat diet (HFD) mice. The results showed that PS treatment reduced the accumulation of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the serum of HFD mice, while increasing the serum levels of high-density lipopro ...[more]

PMID: 37151603

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Project description:BackgroundRheumatoid arthritis (RA) is a long-term autoimmune disorder characterized by chronic inflammation that results in swollen and painful joints and even cartilage and bone damage. The gut microbiota, a novel anti-inflammatory target, is considered an important environmental factor in the development of RA. S-propargyl-cysteine (SPRC), an amino acid analogue, exerts anti-inflammatory, cardioprotective effects, and neuroprotective effects on various diseases. In recent studies, an SPRC treatment exerted anti-inflammatory effects on RA. Meanwhile, gut microbiome dysbiosis in individuals with RA has also been reported by many researchers. However, the relationship between SPRC and gut microbiota in individuals with RA remains unclear.MethodsThirty male Sprague-Dawley (SD) rats were randomly divided into three groups of 10 each, including the Control, Model, and SPRC groups. Adjuvant-induced arthritis (AIA) rats in SPRC group were treated with SPRC. Measurement of paw volume and serum tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels were applied to evaluate the inflammatory status. Fecal samples were collected on the 14th day and 28th day. Gut microbiota were analyzed using 16S ribosomal RNA (rRNA) gene amplicon sequencing. Untargeted metabolomics on plasma samples was applied to investigate the metabolic changes induced by the altered gut microbiota by using derivatization-UHPLC-Q-TOF/MS.FindingsUsing 16S rRNA amplicon sequencing, we found that SPRC significantly altered the gut microbiota structure in AIA rats. In particular, Bifidobacterium, a genus of BSH (Bile Salt Hydrolase)-producing microbes, was overrepresented in SPRC-treated AIA rats. Additionally, a subsequent metabolomics analysis indicated that bile acid metabolism was also altered by SPRC treatment. Interestingly, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), which are formed with the participation of BSH-producing microbes in the intestine, were identified as crucial biomarkers responding to SPRC treatment with significantly lowered levels.InterpretationA mechanistic link between the gut microbiota and plasma metabolites was revealed in this study, which provides insights into the mechanism of SPRC treatment for RA from the perspective of the gut microbiota.

Project description:Autophagic activation in immune cells, gut microbiota dysbiosis, and metabolic abnormalities have been reported separately as characteristics of systemic lupus erythematosus (SLE). Elucidating the crosstalk among the immune system, commensal microbiota, and metabolites is crucial to understanding the pathogenesis of autoimmune diseases. Emerging evidence shows that basophil activation plays a critical role in the pathogenesis of SLE; however, the underlying mechanisms remain largely unknown. Here, we investigated the effects of autophagic inhibition on the pathogenesis of basophils in SLE using Autophagy-related gene 5 (Atg5) knockout (Atg5-/-) as an autophagic inhibitor. Specifically, we knocked out basophilic Atg5 in vivo to investigate its impact on lupus metabolism. Furthermore, Atg5-/- basophils were transferred to basophil-depleted MRL/MpJ-Faslpr (MRL/lpr) mice to study their effect on disease metabolism. Metagenomic and targeted metabolomic sequencing results indicated considerable reduction in the levels of plasma autoantibodies and inflammatory cytokines in the Atg5-/- basophil transfer group compared with that in the control group. Transplanting Atg5-/- basophils improved the gut microbiota balance in MRL/lpr mice, increasing the abundance of beneficial bacteria, such as Ligilactobacillus murinus and Faecalitalea rodentium, and reducing that of potentially pathogenic bacteria such as Phocaeicola salanitronis. The transplantation of Atg5-deficient basophils improved lupus symptoms by modulating lipid and amino acid metabolism. This improvement was linked to changes in the gut microbiota, particularly an increase in Ligilactobacillus murinus and Faecalitalea rodentium populations. These microbial shifts are believed to promote the production of beneficial metabolites, such as γ-linolenic acid and oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine, while reducing the levels of harmful metabolites such as arginine. These alterations in the metabolic profile contribute to the alleviation of lupus symptoms. Collectively, these findings reveal a novel role of basophil autophagy in SLE, highlighting its potential as a therapeutic target.

Dataset Information

Phytosterols Alleviate Hyperlipidemia by Regulating Gut Microbiota and Cholesterol Metabolism in Mice.

Publications

Phytosterols Alleviate Hyperlipidemia by Regulating Gut Microbiota and Cholesterol Metabolism in Mice.

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