ArticleEBioMedicine2018
Dysregulated bile acid signaling contributes to the neurological impairment in murine models of acute and chronic liver failure.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Bile Acids Transporters of Enterohepatic Circulation for Targeted Drug Delivery.Molecules (Basel, Switzerland) · 2022Pooled it
- Lithocholic acid alleviates fatty liver in mice and non-human primate macaques.Life metabolism · 2026Article
- The effects of a diet based on vegetable and dairy protein on nutritional status and MELD score in patients with liver cirrhosis: a randomized controlled study.BMC nutrition · 2026Article
- Animal models accurately representing acute liver failure (Review).International journal of molecular medicine · 2026Review
- Covert hepatic encephalopathy in cirrhosis: implications for early diagnosis and appropriate management.Clinical journal of gastroenterology · 2026Review
- Lacticaseibacillus casei Zhang modulates iron homeostasis in iron-overloaded mice via an IL-22-dependent pathways.NPJ science of food · 2026Article
- Early risperidone exposure impairs cognitive function by perturbation of the gut microbiome and bile acids/tyrosine-PTP1B axis.Microbiome · 2026Article
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Dietary cholesterol impairs cognition via gut microbiota-derived deoxycholic acid in obese mice.Gut microbes · 2025Article
- Enteronephrohepatic circulation of bile acids and therapeutic potential of systemic bile acid transporter inhibitors.Journal of hepatology · 2025Review
- Conjugated bile acids in serum reflect disease severity and predict survival in chronic liver disease of humans and rats.Scientific reports · 2025Article
- Antimicrobial and Anticancer Activities ofNutrients · 2025Article
- Cholic acid as a treatment for cerebrotendinous xanthomatosis: a comprehensive review of safety and efficacy.Orphanet journal of rare diseases · 2025Review
- Dysregulation of bile acid signal transduction causes neurological dysfunction in cirrhosis rats.World journal of hepatology · 2025Article
- Unlocking therapeutic potential of amlexanox in MASH with insights into bile acid metabolism and microbiome.Npj gut and liver · 2025Article
- Research progress on the interaction between multiple organ-brain axes and perioperative neurocognitive disorders: a narrative review.Frontiers in aging neuroscience · 2025Review
- Gut microbial metabolism in Alzheimer's disease and related dementias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Feeding gut microbes to nourish the brain: unravelling the diet-microbiota-gut-brain axis.Nature metabolism · 2024Review
- Increased intestinal bile acid absorption contributes to age-related cognitive impairment.Cell reports. Medicine · 2024Article
- Metabolic phenotyping reveals an emerging role of ammonia abnormality in Alzheimer's disease.Nature communications · 2024Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundHepatic encephalopathy (HE), a severe neuropsychiatric complication, is associated with increased blood levels of ammonia and bile acids (BAs). We sought to determine (1) whether abnormally increased blood BAs in liver cirrhotic patients with HE is caused by elevation of apical sodium-dependent BA transporter (ASBT)-mediated BA reabsorption; and (2) whether increased BA reabsorption would exacerbate ammonia-induced brain injuries.
methodsWe quantitatively measured blood BA and ammonia levels in liver cirrhosis patients with or without HE and healthy controls. We characterized ASBT expression, BA profiles, and ammonia concentrations in a chronic liver disease (CLD) mouse model induced by streptozotocin-high fat diet (STZ-HFD) and an azoxymethane (AOM) - induced acute liver failure (ALF) mouse model. These two mouse models were treated with SC-435 (ASBT inhibitor) and budesonide (ASBT activator), respectively.
findingsBlood concentrations of ammonia and conjugated BAs were substantially increased in cirrhotic patients with HE (n = 75) compared to cirrhotic patients without HE (n = 126). Pharmacological inhibition of the enterohepatic BA circulation using a luminal- restricted ASBT inhibitor, SC-435, in mice with AOM-induced ALF and STZ-HFD -induced CLD effectively reduced BA and ammonia concentrations in the blood and brain, and alleviated liver and brain damages. Budesonide treatment induced liver and brain damages in normal mice, and exacerbated these damages in AOM-treated mice.
interpretationASBT mediated BA reabsorption increases intestinal luminal pH and facilitates conversion of intestinal ammonium to ammonia, leading to abnormally high levels of neurotoxic ammonia and cytotoxic BAs in the blood and brain. Inhibition of intestinal ASBT with SC-435 can effectively remove neurotoxic BAs and ammonia from the bloodstream and thus, mitigate liver and brain injuries resulting from liver failure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.