ArticleNature medicine2025
The gut-brain axis underlying hepatic encephalopathy in liver cirrhosis.
Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association between PNPLA3 rs738409 and susceptibility to etiology-specific liver cirrhosis: a systematic review and meta-analysis.BMC medical genomics · 2026Pooled it
- The role of systemic inflammation in hepatic encephalopathy: advances in inflammatory mechanisms, prevention and treatment research.Annals of medicine · 2026Review
- [Pathogenic mechanisms and advances in the diagnosis and treatment of co-occurring psychiatric and psychological symptoms in patients with liver cirrhosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Disrupted Gut Viral-Bacterial Ecology of Patients With Liver Cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Interorgan Crosstalk in MASLD: A Narrative Review.Biomedicines · 2026Review
- Gut microbiota in health and disease.Molecular biomedicine · 2026Review
- Alterations in the Gut Microbiota of Cirrhotic Patients With Sarcopenia and PH After TIPS.Clinical and translational gastroenterology · 2026Article
- Parabacteroides goldsteinii and its metabolite 7-KLCA attenuate endometriosis via TGR5 to reprogram macrophages by modulating the PPARγ/GPR132 axis.NPJ biofilms and microbiomes · 2026Article
- Enterococcus hirae QT4713-derived dopamine ameliorates intestinal inflammation and MPTP-induced Parkinson's disease in mice.NPJ Parkinson's disease · 2026Article
- TIPS in Older Adults: Reserve-Based Risk Stratification and Practical Approach.Journal of clinical medicine · 2026Review
- Puerarin Alleviates Depression via Integrated Regulation of TLR4/MyD88/NF-κB Signaling and Gut Microbiota-Metabolic Axis.Neurochemical research · 2026Article
- Research progress of blood-brain barrier penetrating and brain diseases therapy by natural biopolymer - based nanomedicine delivery systems.Materials today. Bio · 2026Review
- [Research advances on hepatic encephalopathy following transjugular intrahepatic portosystemic shunt].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Activation of SNr GABA neurons drives liver-brain-eye axis dysfunction in hepatic encephalopathy.iScience · 2026Article
- The Gut-Liver Axis in MASLD: From Host-Microbiome Crosstalk to Precision Therapeutics.Microorganisms · 2026Review
- Navigating TIPS in the era of ageing and metabolic comorbidity: a contemporary narrative review of risk, resilience, and outcomes.Gastroenterology report · 2026Review
- [Research progress in the field of liver failure with artificial livers in 2025].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Development of a tryptophan metabolomics-based diagnostic model for hepatic encephalopathy in liver cirrhosis.European journal of medical research · 2026Article
- AI digital-twin ecosystem translating gut-microbiome-neuroimmune signals into precision sleep-mood interventions.Frontiers in psychiatry · 2026Review
- Fecal microbiota transplantation: from empirical remedy to precision medicine.Frontiers in microbiomes · 2026Review
Corrections and comments
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Authors and funding
31 authors.
Funding
Abstract
Up to 50-70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut-brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus, increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R. gnavus showed brain phenylethylamine (PEA) accumulation, along with memory impairment, symmetrical tremors and cortex-specific neuron loss, typically found in patients with HE. This accumulation of PEA was primarily driven by decreased monoamine oxidase-B activity in both the liver and serum due to cirrhosis. Targeting PDC or PEA reversed the neurological symptoms induced by R. gnavus. Furthermore, fecal microbiota transplantation from patients with HE to germ-free cirrhotic mice replicated these symptoms and further corroborated the efficacy of targeting PDC or PEA. Clinically, high baseline PEA levels were linked to a sevenfold increased risk of HE after intrahepatic portosystemic shunt procedures. Our findings expand the understanding of the gut-liver-brain axis and identify a promising therapeutic and predictive target for HE.
Indexed as
Identifiers
39779925What Socratic holds
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 Socratic graph.