Background and AimsType 2 Diabetes mellitus (T2DM) has reached an epidemic status worldwide. Targeting bile acid signaling has therapeutic potential for treating T2DM. However, the effect of bile acid on T2DM and related mechanisms remains unclear. Here, we explored the role of bile acid in T2DM and elucidated the mechanisms involved.MethodsWe established an STZ-induced rat model of T2DM and divided it into an bile acid-treated group and saline control group according to the random number table method. We incubated the bile acid-treated group with human bile acid via middle small intestine intubation and the saline control group was incubated with the same amount of normal saline. We compared the fasting body mass, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2h-PG), fasting plasma insulin (FINS), fasting plasma triglyceride (TG), cholesterol, and total bile acid levels between the two groups one week before surgery and one to four weeks after surgery. Mechanically, Western blot, IHC, and ELISA assays were employed to detect the effect of bile acid on the TGR5/GLP-1 and FXR/FGF15 pathways.ResultsBile acid injection could increase the FINS level and decrease the 2h-PBG level of T2DM rats. In addition, bile acid injection did not affect FBG, fasting body mass, TG, CH, and total bile acid. At the same time, bile acid injection could activate the TGR5/GLP-1 pathway but could not influence the FXR/FGF15 pathway.ConclusionBile acids treatment promotes glucose homeostasis in the STZ-induced T2MD rat model via the following mechanism by activating the TGR5/GLP-1 signaling pathway rather than FXR/FGF15 pathway to improve glucose tolerance and thus achieve glucose homeostasis. The bile acid/TGR5/GLP-1 signaling pathway may be a crucial mechanism of controlling the blood glucose of T2DM rats, and TGR5/GLP-1 pathway may constitute novel targets for treating T2DM.

01 May 2024·Journal of Advanced Research

Bile acid and nonalcoholic steatohepatitis: Molecular insights and therapeutic targets

Review

Author: Schnabl, Bernd ; Yang, Ling ; Chu, Huikuan ; Cheng, Zilu ; Chen, Yixiong

BACKGROUNDNonalcoholic steatohepatitis (NASH) has been the second most common cause of liver transplantation in the United States. To date, NASH pathogenesis has not been fully elucidated but is multifactorial, involving insulin resistance, obesity, metabolic disorders, diet, dysbiosis, and gene polymorphism. An effective and approved therapy for NASH has also not been established. Bile acid is long known to have physiological detergent function in emulsifying and absorbing lipids and lipid-soluble molecules within the intestinal lumen. With more and more in-depth understandings of bile acid, it has been deemed to be a pivotal signaling molecule, which is capable of regulating lipid and glucose metabolism, liver inflammation, and fibrosis. In recent years, a plethora of studies have delineated that disrupted bile acid homeostasis is intimately correlated with NASH disease severity.AIMSThe review aims to clarify the role of bile acid in hepatic lipid and glucose metabolism, liver inflammation, as well as liver fibrosis, and discusses the safety and efficacy of some pharmacological agents targeting bile acid and its associated pathways for NASH.KEY SCIENTIFIC CONCEPTS OF REVIEWBile acid has a salutary effect on hepatic metabolic disorders, which can ameliorate liver fat accumulation and insulin resistance mainly through activating Takeda G-protein coupled receptor 5 and farnesoid X receptor. Moreover, bile acid also exerts anti-inflammation and anti-fibrosis properties. Furthermore, bile acid has great potential in nonalcoholic liver disease stratification and treatment of NASH.

01 Jan 2024·Gastro Hep Advances

The Roles of Gut Microbiota Metabolites in the Occurrence and Development of Colorectal Cancer: Multiple Insights for Potential Clinical Applications

Review

Author: Cheng, Wenyue ; Yang, Rongcun ; Li, Fan

Colorectal cancer (CRC) is one of the most common cancers worldwide. The occurrence and development of CRC are related to multiple risk factors such as gut microbiota. Indeed, gut microbiota plays an important role in the different phases of colorectal cancers (CRCs) from oncogenesis to metastasis. Some specific bacteria such as Fusobacterium nucleatum (F. nucleatum) associated with CRCs have been found. However, recently identified bile acid and tryptophan metabolites as well as short chain fatty acids (SCFAs), which are derived from gut microbiota, can also exert effects on the CRCs such as that SCFAs directly inhibit CRC growth. Importantly these metabolites also modulate immune responses to affect CRCs. They not only act as tumor inhibiting factor(s) but also promotor(s) in the occurrence, development, and metastasis of CRCs. While gut microbiota metabolites (GMMs) inhibit immunity against CRCs, some of them also improve immune responses to CRCs. Notably, GMMs also potentially affect the shaping of immune-privileged metastatic niches through direct roles or immune cells such as macrophages and myeloid-derived suppressive cells. These findings offer new insights for clinical application of gut microbiota in precise and personalized treatments of CRCs. Here, we will mainly discuss direct and indirect (via immune cells) effects of GMMs, especially SCFAs, bile acid and tryptophan metabolites on the occurrence, development and metastasis of CRCs.

100 Deals associated with Bile Acid Oligomers(Panjab University)

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Indication	Highest Phase	Country/Location	Organization	Date
Staphylococcus Aureus Infections	Discovery	IN	Punjabi University	13 Nov 2018

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