Glycoursodeoxycholic acid regulates bile acids level and alters gut microbiota and glycolipid metabolism to attenuate diabetes

Chen, Bingting; Bai, Yu; Tong, Fenglian; Yan, Junlin; Zhang, Rui; Zhong, Yewei; Tan, Huiwen; Ma, Xiaoli

doi:10.1080/19490976.2023.2192155

Cited by 35 publications

(12 citation statements)

References 47 publications

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“…20 Our previous study, along with other publications, had also verified that GUDCA maintained metabolic homeostasis and ameliorated metabolic disorders including atherosclerosis, diabetes, and fatty liver disease. [19][20][21][22]66 In this study, we aimed to investigate the potential association between plasma GUDCA levels and thrombotic tendency. Our clinical cohort revealed a considerable decline in plasma GUDCA levels among patients with various types of arterial thrombotic diseases, including ACS, IS, and PVAT.…”

Section: Discussionmentioning

confidence: 99%

Glycoursodeoxycholic Acid Alleviates Arterial Thrombosis via Suppressing Diacylglycerol Kinases Activity in Platelet

Yang,

Feng,

Peng

et al. 2024

ATVB

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BACKGROUND: Glycoursodeoxycholic acid (GUDCA) has been acknowledged for its ability to regulate lipid homeostasis and provide benefits for various metabolic disorders. However, the impact of GUDCA on arterial thrombotic events remains unexplored. The objective of this study is to examine the effects of GUDCA on thrombogenesis and elucidate its underlying mechanisms. METHODS: Plasma samples from patients with arterial thrombotic events and diet-induced obese mice were collected to determine the GUDCA concentrations using mass spectrometry. Multiple in vivo murine thrombosis models and in vitro platelet functional assays were conducted to comprehensively evaluate the antithrombotic effects of GUDCA. Moreover, lipidomic analysis was performed to identify the alterations of intraplatelet lipid components following GUDCA treatment. RESULTS: Plasma GUDCA level was significantly decreased in patients with arterial thrombotic events and negatively correlated with thrombotic propensity in diet-induced obese mice. GUDCA exhibited prominent suppressing effects on platelet reactivity as evidenced by the attenuation of platelet activation, secretion, aggregation, spreading, and retraction ( P <0.05). In vivo, GUDCA administration robustly alleviated thrombogenesis ( P <0.05) without affecting hemostasis. Mechanistically, GUDCA inhibited DGK (diacylglycerol kinase) activity, leading to the downregulation of the phosphatidic acid–mediated signaling pathway. Conversely, phosphatidic acid supplementation was sufficient to abolish the antithrombotic effects of GUDCA. More importantly, long-term oral administration of GUDCA normalized the enhanced DGK activity, thereby remarkably alleviating the platelet hyperreactivity as well as the heightened thrombotic tendency in diet-induced obese mice ( P <0.05). CONCLUSIONS: Our study implicated that GUDCA reduces platelet hyperreactivity and improves thrombotic propensity by inhibiting DGKs activity, which is a potentially effective prophylactic approach and promising therapeutic agent for arterial thrombotic events.

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Section: Discussionmentioning

confidence: 99%

Glycoursodeoxycholic Acid Alleviates Arterial Thrombosis via Suppressing Diacylglycerol Kinases Activity in Platelet

Yang,

Feng,

Peng

et al. 2024

ATVB

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“…Under the action of 7α-hydroxylase and bile acid saltolytic enzyme, primary bile acids transform into secondary bile acids while simultaneously activating a range of nuclear receptors, including the nuclear farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor 1 (TGR5), thus facilitating both hepatic synthesis and intestinal reabsorption of bile acid. They additionally play significant roles in glucose, lipid, and energy metabolism ( Liu et al., 2020 ; Zhao et al., 2020 ; Gao et al., 2022 ; Chen et al., 2023 ; Collins et al., 2023 ). Traussnigg et al.…”

Section: Role Of Gut Microbiota In the Pathophysiology Of Dmmentioning

confidence: 99%

“…Furthermore, the glucose and insulin tolerance test results, insulin levels, and HOMA-IR index of experimental mice were reduced. GUDCA increases the levels of taurine cholic acid and the abundance of Bacteroides vulgaris in mice, activating TGR5 and upregulating the expression of UCP-1, which leads to increased thermogenesis in white adipose tissue and induction of intestinal GLP-1 secretion ( Chen et al., 2023 ). Therefore, disturbances in the gut microbiota can reduce the formation of bile acids, hinder the production of free and secondary bile acids ( Fang et al., 2022 ), and weaken the activation of the FXR, resulting in abnormal glucose metabolism.…”

Section: Role Of Gut Microbiota In the Pathophysiology Of Dmmentioning

confidence: 99%

“…Therefore, disturbances in the gut microbiota can reduce the formation of bile acids, hinder the production of free and secondary bile acids ( Fang et al., 2022 ), and weaken the activation of the FXR, resulting in abnormal glucose metabolism. Furthermore, the activation of the TGR5 receptor is weakened, which leads to a decrease in thyroid hormone thermogenesis, GLP-1 levels, and insulin secretion and an increase in blood sugar levels ( Massey and Brown, 2021 ; Xia et al., 2021 ; Chen et al., 2023 ; Makki et al., 2023 ). As a metabolite, the reduction of bile acid ( Fang et al., 2022 ) aggravates this enteric dysbacteriosis and forms a cycle that seriously affects the normal metabolic signaling pathways and leads to the occurrence of DM ( Canfora et al., 2022 ).…”

Section: Role Of Gut Microbiota In the Pathophysiology Of Dmmentioning

confidence: 99%

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Advances in fecal microbiota transplantation for the treatment of diabetes mellitus

Zhang,

Wang,

Liu

et al. 2024

Front. Cell. Infect. Microbiol.

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Diabetes mellitus (DM) refers to a group of chronic diseases with global prevalence, characterized by persistent hyperglycemia resulting from various etiologies. DM can harm various organ systems and lead to acute or chronic complications, which severely endanger human well-being. Traditional treatment mainly involves controlling blood sugar levels through replacement therapy with drugs and insulin; however, some patients still find a satisfactory curative effect difficult to achieve. Extensive research has demonstrated a close correlation between enteric dysbacteriosis and the pathogenesis of various types of DM, paving the way for novel therapeutic approaches targeting the gut microbiota to manage DM. Fecal microbiota transplantation (FMT), a method for re-establishing the intestinal microbiome balance, offers new possibilities for treating diabetes. This article provides a comprehensive review of the correlation between DM and the gut microbiota, as well as the current advancements in FMT treatment for DM, using FMT as an illustrative example. This study aims to offer novel perspectives and establish a theoretical foundation for the clinical diagnosis and management of DM.

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“…Among various human body metabolites processed by GM, bile acids (BAs), synthesized mainly in the liver, have attracted more and more attention because of their known tumor-promoting properties ( 9 ). Besides, T2DM patients with high BAs tend to have more severe metabolic disorders ( 10 ). Given the known interaction among GM-BA, it would be interesting to investigate the role of GM-BA interactions in affecting T2DM+HCC disease progress.…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus brevis alleviates the progress of hepatocellular carcinoma and type 2 diabetes in mice model via interplay of gut microflora, bile acid and NOTCH 1 signaling

et al. 2023

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Type 2 diabetes (T2DM) clinically exhibits a higher incidence of hepatocellular carcinoma (HCC), contributing to a lousy prognosis in patients harboring both diseases. Microflora-based therapy draws attention with low side effects. Accumulating evidence shows that Lactobacillus brevis can improve blood glucose and body weight of the T2DM mice model and reduce several cancer incidences. However, the therapeutic effect of Lactobacillus brevis in affecting the prognosis of T2DM+HCC remains unknown. In this study, we aim to explore this question via an established T2DM+HCC mice model. We observed a significant alleviation after the probiotic intervention. Lactobacillus brevis improves blood glucose and insulin resistance and ameliorates Mechanically. Combined with a multi-omics approach including 16SrDNA, GC-MS, and RNA-seq, we identified distinct intestinal microflora composition and metabolites after Lactobacillus brevis intervention. Furthermore, we found that Lactobacillus brevis delayed disease progression by regulating MMP9 and NOTCH 1 signaling pathways, potentially through gut microflora and BA interaction. This study indicates that Lactobacillus brevis may improve the prognosis of T2DM + HCC, providing novel therapeutic opportunities via targeting intestinal flora for patients with T2DM+HCC.

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Glycoursodeoxycholic acid regulates bile acids level and alters gut microbiota and glycolipid metabolism to attenuate diabetes

Cited by 35 publications

References 47 publications

Glycoursodeoxycholic Acid Alleviates Arterial Thrombosis via Suppressing Diacylglycerol Kinases Activity in Platelet

Glycoursodeoxycholic Acid Alleviates Arterial Thrombosis via Suppressing Diacylglycerol Kinases Activity in Platelet

Advances in fecal microbiota transplantation for the treatment of diabetes mellitus

Lactobacillus brevis alleviates the progress of hepatocellular carcinoma and type 2 diabetes in mice model via interplay of gut microflora, bile acid and NOTCH 1 signaling

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