Bile Acids in Hepatic Encephalopathy

Abstract

TX 76504, USA and y Central Texas Veterans Healthcare System, Temple, TX 76504, USA Hepatic encephalopathy describes the array of neurological complications that arise due to liver insufficiency and/or portal-systemic shunt. The pathogenesis of hepatic encephalopathy shares a longstanding association with hyperammonemia and inflammation. Recently, aberrant bile acid signaling has been implicated in the development of key features of hepatic encephalopathy due to acute liver failure including neuronal dysfunction, neuroinflammation and blood-brain barrier permeability. This review summarizes the findings of recent studies demonstrating a role for bile acids in hepatic encephalopathy and speculates on the possible downstream consequences of bile acid signaling. ( J CLIN EXP HEPATOL 2019;9:117-124) Keywords: blood-brain barrier, farnesoid X receptor, neuroinflammation, sphingosine-1-phosphate receptor 2, Takeda G-protein coupled receptor 5 (TGR5)

Identifying differences in bile acid pathways for cholesterol clearance in Alzheimer’s disease using metabolic networks of human brain regions

“…Bile acids were quantified from 111 post-mortem brain samples from the dorsolateral prefrontal cortex of AD, MCI and CN individuals in the ROSMAP study Expressed in brain (https://www.synapse.org/#!Synapse:syn10235594) (Supplementary file 2). Although the genes involved in production of cholic acid were not expressed in the brain samples, detection of cholic acid from the metabolomics analysis suggested that cholic acid might enter the brain from the periphery as previously shown in other studies 20,28,29 . We compared the levels of primary and secondary bile acids in individuals with CERAD score of 1-4, where 1, 2, 3 and 4 indicate definitive AD, probable AD, possible AD and no evidence of AD, respectively.…”

Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer’s Disease

“…Although the genes involved in the production of CA were not expressed in the brain samples, the detection of CA from the metabolomics analysis suggested that CA may enter the brain from the periphery, as previously shown in other studies. 20 , 28 , 29 We compared the levels of primary and secondary BAs in individuals with a Consortium to Establish a Registry for Alzheimer's Disease (CERAD) score of 1–4, in which 1, 2, 3, and 4 indicate definitive AD, probable AD, possible AD, and no evidence of AD, respectively. The ratio of primary conjugated and secondary BAs with respect to CA showed that deoxycholic acid (DCA), lithocholic acid (LCA), glycochenodeoxycholate (GCDCA), CDCA, taurodeoxycholic acid (TDCA), glycodeoxycholic acid (GDCA), ursodeoxycholic acid (UDCA), allolithocholate (alloLCA) and taurocholic acid (TCA) were higher in individuals with AD (CERAD score 1–3) compared to controls ( Figure 4 ).…”

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

“…The brain microenvironment loses stability, followed by BBB dysfunction. Moreover, multiple factors disturb the CNS function, including changes in brain structure, neurotransmitters, and other substance concentrations, leading to cognitive impairments in HE ( Jones, 2003 ; Banks, 2006 ; Dhanda and Sandhir, 2015 ; Jayakumar and Norenberg, 2018 ; DeMorrow, 2019 ).…”

“…However, bile acid levels were found to be increased in the cerebrospinal fluid, while toxic bile acids accumulated in the brains of the BDL mouse models. Therefore, nervous system disorders are associated with the toxic effects of bile acids in HE ( Weiss et al, 2016 ; DeMorrow, 2019 ).…”