Author: Li, Jiatian ; Wang, Yilun ; Doherty, Michael ; Zeng, Chao ; Li, Changjun ; Zhang, Yuqing ; Xie, Dongxing ; Sun, Chuying ; Wu, Jing ; Wang, Ning ; Zhang, Weiya ; Li, Hui ; Gonzalez, Frank J. ; Xie, Cen ; Wang, Tingjian ; Huang, Xi ; Yang, Zidan ; Lei, Guanghua ; Yang, Tuo ; Yang, Yuanheng ; Wei, Jie ; Jiao, Tingying ; Zhang, Mengjiao ; Hao, Cong

Whether a gut-joint axis exists to regulate osteoarthritis is unknown. In two independent cohorts, we identified altered microbial bile acid metabolism with reduced glycoursodeoxycholic acid (GUDCA) in osteoarthritis. Suppressing farnesoid X receptor (FXR)—the receptor of GUDCA—alleviated osteoarthritis through intestine-secreted glucagon-like peptide 1 (GLP-1) in mice. GLP-1 receptor blockade attenuated these effects, whereas GLP-1 receptor activation mitigated osteoarthritis. Osteoarthritis patients exhibited a lower relative abundance of Clostridium bolteae , which promoted the formation of ursodeoxycholic acid (UDCA), a precursor of GUDCA. Treatment with C. bolteae and Food and Drug Administration–approved UDCA alleviated osteoarthritis through the gut FXR–joint GLP-1 axis in mice. UDCA use was associated with lower risk of osteoarthritis-related joint replacement in humans. These findings suggest that orchestrating the gut microbiota–GUDCA–intestinal FXR–GLP-1–joint pathway offers a potential strategy for osteoarthritis treatment.

01 Apr 2025·Journal of Dairy Science

Supplementation with ursodeoxycholic acid and bile salt benefits lactation performance, health, and rumen and fecal microbiota of transition dairy cows

Article

Author: Liu, Jian-Xin ; Guo, Zhi-Yao ; Che, Hao-Yu ; Gu, Feng-Fei ; Sun, Hui-Zeng ; Wu, Fang-Chao ; Fan, Fei-Xiang ; Yang, Kai-Lun

This study investigated the effects of ursodeoxycholic acid (UDCA) and bile salt (BAS) supplementation on lactation performance, health, and gut microbiota in periparturient dairy cows. Fifty-one Holstein dairy cows were selected at d -28 before parturition and blocked into 3 dietary treatments, including the control (CON; n = 17) received a basal diet, whereas the UDCA (n = 17) and BAS groups (n = 17) were supplemented with 10 g/d UDCA and 20 g/d BAS from d -21 to +21, with an observation phase until d +35. Milk yield and composition were recorded weekly, whereas the DMI were measured biweekly. Blood samples were collected at d +7 and +21, whereas rumen fluid and fecal samples were collected at d +21. Milk yield was significantly higher in the UDCA group at d +21 compared with the CON group, whereas on d +28, milk yield was significantly higher in both the UDCA and BAS groups compared with the CON group, and the DMI of the UDCA group showed an increased tendency at prepartum. Plasma nonesterified fatty acids were significantly higher in the BAS group, whereas Ala aminotransferase content were significantly lower in the UDCA group compared with the control. Furthermore, the cholesterol, malondialdehyde, oxidative stress index, serum amyloid A, and haptoglobin content were significantly lower in the UDCA and BAS groups. In total, 35, 43, and 45 plasma bile acids (BA) were detected in the control, UDCA, and BAS groups, respectively. Compared with the control, 8 key BA, including UDCA, tauroursodeoxycholic acid, glycoursodeoxycholic acid, and 5 key BA, including tauro-β-muricholic acid and hyocholic acid, were identified in the UDCA and BAS groups, respectively. The concentrations of total VFA and acetate in the UDCA and BAS groups was higher than that in the CON group, and the concentration of propionate tended to be higher. The β-diversity of both rumen and gut microbiota was significantly higher in the CON, UDCA, and BAS groups, whereas no significant changes were observed in α-diversity. Key rumen VFA-production bacteria, including Prevotella_7, Succinivibrionaceae_UCG-001, and Selenomonas, were enriched in the UDCA and BAS groups, along with an increase in beneficial gut microbiota, such as Butyrivibrio, Ruminococcus, and Caproiciproducen, and a reduction in harmful bacteria, such as Stenotrophomonas and Chryseobacterium. These findings suggest that the observed improvements in production performance and health may be mediated by alterations in peripheral BA and rumen and gut microbiota, offering insights for optimizing the nutrition and health of transitional dairy cows.

01 Feb 2025·International Immunopharmacology

Dual GIP and GLP-1 receptor agonist tirzepatide alleviates hepatic steatosis and modulates gut microbiota and bile acid metabolism in diabetic mice

Article

Author: Zhu, Yikun ; Gan, Lu ; Zhang, Gerong ; Liu, Jing ; Yang, Fan ; Cheng, Rui ; Hu, Weiting ; Qin, Weiwei ; Gao, Ying ; Li, Xing ; Gong, Wenyu

Tirzepatide is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors and is a promising therapeutic option for type 2 diabetes mellitus (T2DM). Nevertheless, its effect and underlying mechanism on hepatic steatosis remain ambiguous. Herein, we explored the impact of tirzepatide on improving hepatic steatosis in diabetic mice, with a particular focus on the gut microbiota and bile acids (BAs) using animal models. The tirzepatide effectively reduced body weight, improved insulin resistance, decreased serum and hepatic lipid levels, and mitigated liver injury. Compared to semaglutide, tirzepatide exhibited superior efficacy in reducing hepatic lipid accumulation. 16S rRNA gene sequencing and targeted metabolomics of BAs revealed that tirzepatide ameliorated gut microbiota dysbiosis and BAs metabolism in diabetic mice. Notably, tirzepatide observably increased the abundance of beneficial genera such as Akkermansia, elevated the ratio of farnesoid X receptor (FXR) antagonists (glycoursodeoxycholic acid: GUDCA, β-muricholic acid: β-MCA, hyodeoxycholic acid: HDCA, ursodeoxycholic acid: UDCA) to natural agonists (cholic acid: CA, lithocholic acid: LCA, chenodeoxycholic acid: CDCA, glycocholic acid: GCA, taurodeoxycholic acid: TDCA), and reduced FXR expression in intestinal tissues. In conclusion, tirzepatide attenuated hepatic steatosis in diabetic mice and regulated the gut microbiota and BAs metabolism, which may help to provide a novel therapeutic approach and therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD).

100 Deals associated with Glycoursodeoxycholic Acid

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Arterial thrombosis	Preclinical	China	the First Affiliated Hospital of Sun Yat-Sen University	01 Jun 2024

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

Glycoursodeoxycholic Acid

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation