The gut-liver axis in progressive steatotic liver disease
The gut-liver axis regulates metabolic homeostasis, with bile acids (BAs) serving as key signalling molecules. BA dysregulation is implicated in metabolic dysfunction-associated steatotic liver disease (MASLD)and metabolic dysfunction- and alcohol-associated liver disease (MetALD), yet consistent id...
| Authors: | , , , , , , , , , , , |
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| Format: | article |
| Publication Date: | 2025 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:ddd.uab.cat:320308 |
| Online Access: | https://ddd.uab.cat/record/320308 https://dx.doi.org/urn:doi:10.1016/j.jnha.2025.100671 |
| Access Level: | Open access |
| Keyword: | Bile acids Gut-liver axis Liver disease Gut microbiome Metabolomics |
| Summary: | The gut-liver axis regulates metabolic homeostasis, with bile acids (BAs) serving as key signalling molecules. BA dysregulation is implicated in metabolic dysfunction-associated steatotic liver disease (MASLD)and metabolic dysfunction- and alcohol-associated liver disease (MetALD), yet consistent identification of BA markers and their mechanistic roles across different stages of these diseases remain elusive. Methods: We integrated three complementary studies to examine BA dysregulation: a population-based cohort (1522 females from TwinsUK with serum BA and liver biomarker data), a clinical cohort (30 patients with steatotic liver disease, fibrosis stages F0-F4, and 4 controls), and rodent models (20 rats with MASLD/MetALD vs.9 controls). BA profiles were quantified via LC-MS. Results: The primary bile acid taurocholate was consistently correlated with liver pathology: in TwinsUK, it associated with ALT (β [95%CI] 1.81 [1.27, 2.36], FDR < 0.05) both overall and when stratifying for age (<65 years, n = 923; ≥65 years, n = 599); in the clinical cohort, it was associated with F3 fibrosis (OR [95%CI] 8.56 × 10 10 [3.80 × 10 13, 1.93 × 10 6], FDR < 0.05); and in rodents, it was associated with MASLD/MetALD (OR [95%CI] 2.86 [1.17, 9.51], FDR < 0.05). The secondary bile acid taurochenodeoxycholate was associated with both early (F0, OR [95%CI] 13.63 [1.04, 179.17], p < 0.05) and advanced stages of disease (rodents, OR [95% CI] 15.41 [2.94, 311.82], FDR < 0.05).Conclusion: Taurocholate and taurochenodeoxycholate emerge as consistent BA markers across liver disease stages, suggesting BA metabolism as potential therapeutic targets. This multi-model study bridges knowledge gaps in BA-driven mechanisms, informing personalised strategies for SLD management. |
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