Role of Gut Microbiota in Bile-Acid Metabolism

*Yuji Naito, Tomohisa Takagi and Ryo Inoue*

## **Abstract**

The role of the gut microbiota in modifying the pathophysiology of various diseases, including neurodegenerative diseases, is increasingly becoming clear. Bile acids have been shown to be endogenous factors that affect gut microbiota, and bile-acid metabolites directly or indirectly affect host physiology and pathophysiology. The development of metagenomic analysis for gut microbiota and systematic bile-acid measurement using LC–MS/MS has triggered a breakthrough for research in this field. Clinically, an inhibitor of the ileal bile-acid transporter (Elobixibat) was used as a therapeutic agent for chronic constipation, which also paved the way for progress in bile-acid signal research. Additionally, this review emphasizes the importance of gut microbiota-bile acid-receptor signals when considering nutritional approaches to promote healthy longevity.

**Keywords:** *Akkermansia muciniphila*, bile acid, gut microbiota, ileal bile-acid transporter, TGR5

#### **1. Introduction**

Bile acids have been studied for more than 100 years, but recently, their interaction with intestinal flora has been drawing attention and is being increasingly clarified. Bile-acid research, which has been conducted mainly in the field of liver disease, has led to the development of ursodeoxycholic acid (UDCA), which is generally accepted to improve clinical and biochemical index values in patients with cholestatic liver disease. TGR5 (G protein-coupled bile-acid receptor 1, GPBAR-1), identified in 2002, is a G protein-coupled receptor with seven transmembrane domains and is widely distributed in various organs and tissues. TGR5 can be activated by primary and secondary bile acids, indicating the function of bile acids as signal transduction molecules and in regulating energy metabolism and glycolipid metabolism [1]. Bile acids undergo various metabolic processes such as deconjugation by intestinal bacteria; it has also been shown that the host response is regulated by the reaction between the metabolite and the receptor [2]. Under these circumstances, an inhibitor of the ileal bile-acid transporter (IBAT) localized at the terminal ileum has been shown to be effective in treating constipation [3, 4] and has become a topic of clinical research. This review focuses on the interaction between bile acids and gut microbiota.
