Role of Microbiota-Modified Bile Acids in the Regulation of Intracellular Organelles and Neurodegenerative Diseases

Abstract

Bile acids (BAs) are amphiphilic steroidal molecules generated from cholesterol in the liver and facilitate the digestion and absorption of fat-soluble substances in the gut. Some BAs in the intestine are modified by the gut microbiota. Because BAs are modified in a variety of ways by different types of bacteria present in the gut microbiota, changes in the gut microbiota can affect the metabolism of BAs in the host. Although most BAs absorbed from the gut are transferred to the liver, some are transferred to the systemic circulation. Furthermore, BAs have also been detected in the brain and are thought to migrate into the brain through the systemic circulation. Although BAs are known to affect a variety of physiological functions by acting as ligands for various nuclear and cell-surface receptors, BAs have also been found to act on mitochondria and autophagy in the cell. This review focuses on the BAs modified by the gut microbiota and their roles in intracellular organelles and neurodegenerative diseases.

Underlying Mechanisms behind the Brain–Gut–Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

“…Finally, bile acids (BAs) are also linked to autophagy and the maintenance of mitochondrial quality control [109].…”

The microbiota-gut-brain-immune interface in the pathogenesis of neuroinflammatory diseases: a narrative review of the emerging literature

“…Bile acids are synthesized from cholesterol. Primary bile acids like chenodeoxycholic acid (CDCA) and cholic acid (CA) are produced first ( 36 ). After production in the liver, primary bile acids are transported by way of the small intestine to the colon where they are metabolized by the gut microbiota into the secondary bile acids such as lithocholic acid (LCA) and deoxycholic acid (DCA) ( 36 ).…”

“…Primary bile acids like chenodeoxycholic acid (CDCA) and cholic acid (CA) are produced first ( 36 ). After production in the liver, primary bile acids are transported by way of the small intestine to the colon where they are metabolized by the gut microbiota into the secondary bile acids such as lithocholic acid (LCA) and deoxycholic acid (DCA) ( 36 ). These secondary bile acids are then transported across the gut barrier where they may travel to the liver or circulate systemically, likely also crossing the blood-brain barrier ( 36 ).…”

“…After production in the liver, primary bile acids are transported by way of the small intestine to the colon where they are metabolized by the gut microbiota into the secondary bile acids such as lithocholic acid (LCA) and deoxycholic acid (DCA) ( 36 ). These secondary bile acids are then transported across the gut barrier where they may travel to the liver or circulate systemically, likely also crossing the blood-brain barrier ( 36 ). While the gut microbiota determines the production of secondary bile acids, secondary bile acids also seem to alter the composition of the gut microbiome, indicating a bidirectional relationship ( 35 , 37 ).…”

Multidirectional associations between the gut microbiota and Parkinson’s disease, updated information from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway

“…Previous studies reported that several bile salt hydrolase-containing bacteria, such as Bacteroides spp. , Bifidobacterium, and Lactobacillus , were enhanced in PD patients ( Spichak et al., 2021 ; Ghezzi et al., 2022 ), indicating a complicated association among PD, microbiota, and BAs ( Kiriyama and Nochi, 2023 ), which is still unclear. Wang et al.…”