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...

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Autores: Louca, Panayiotis, Pericàs, Juan M.|||0000-0002-3645-3293, Lin, Yu, Kouraki, Afroditi, Estévez-Vázquez, Olga, Martínez-Gómez, María, Cusidó, M. Serra, Simpson, Joanna P., Cubero, Francisco Javier, Homer, Natalie Z.M., Valdes, Ana M., Menni, Cristina
Formato: artículo
Fecha de publicación:2025
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:320308
Acesso em linha:https://ddd.uab.cat/record/320308
https://dx.doi.org/urn:doi:10.1016/j.jnha.2025.100671
Access Level:acceso abierto
Palavra-chave:Bile acids
Gut-liver axis
Liver disease
Gut microbiome
Metabolomics
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spelling The gut-liver axis in progressive steatotic liver diseaseA focus on bile acid dysregulationLouca, PanayiotisPericàs, Juan M.|||0000-0002-3645-3293Lin, YuKouraki, AfroditiEstévez-Vázquez, OlgaMartínez-Gómez, MaríaCusidó, M. SerraSimpson, Joanna P.Cubero, Francisco JavierHomer, Natalie Z.M.Valdes, Ana M.Menni, CristinaBile acidsGut-liver axisLiver diseaseGut microbiomeMetabolomicsThe 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. 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/320308https://dx.doi.org/urn:doi:10.1016/j.jnha.2025.100671reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3203082026-06-06T12:50:31Z
dc.title.none.fl_str_mv The gut-liver axis in progressive steatotic liver disease
A focus on bile acid dysregulation
title The gut-liver axis in progressive steatotic liver disease
spellingShingle The gut-liver axis in progressive steatotic liver disease
Louca, Panayiotis
Bile acids
Gut-liver axis
Liver disease
Gut microbiome
Metabolomics
title_short The gut-liver axis in progressive steatotic liver disease
title_full The gut-liver axis in progressive steatotic liver disease
title_fullStr The gut-liver axis in progressive steatotic liver disease
title_full_unstemmed The gut-liver axis in progressive steatotic liver disease
title_sort The gut-liver axis in progressive steatotic liver disease
dc.creator.none.fl_str_mv Louca, Panayiotis
Pericàs, Juan M.|||0000-0002-3645-3293
Lin, Yu
Kouraki, Afroditi
Estévez-Vázquez, Olga
Martínez-Gómez, María
Cusidó, M. Serra
Simpson, Joanna P.
Cubero, Francisco Javier
Homer, Natalie Z.M.
Valdes, Ana M.
Menni, Cristina
author Louca, Panayiotis
author_facet Louca, Panayiotis
Pericàs, Juan M.|||0000-0002-3645-3293
Lin, Yu
Kouraki, Afroditi
Estévez-Vázquez, Olga
Martínez-Gómez, María
Cusidó, M. Serra
Simpson, Joanna P.
Cubero, Francisco Javier
Homer, Natalie Z.M.
Valdes, Ana M.
Menni, Cristina
author_role author
author2 Pericàs, Juan M.|||0000-0002-3645-3293
Lin, Yu
Kouraki, Afroditi
Estévez-Vázquez, Olga
Martínez-Gómez, María
Cusidó, M. Serra
Simpson, Joanna P.
Cubero, Francisco Javier
Homer, Natalie Z.M.
Valdes, Ana M.
Menni, Cristina
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bile acids
Gut-liver axis
Liver disease
Gut microbiome
Metabolomics
topic Bile acids
Gut-liver axis
Liver disease
Gut microbiome
Metabolomics
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/320308
https://dx.doi.org/urn:doi:10.1016/j.jnha.2025.100671
url https://ddd.uab.cat/record/320308
https://dx.doi.org/urn:doi:10.1016/j.jnha.2025.100671
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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