Serum lipidome unravels a diagnostic potential in bile acid diarrhoea

Objective: Bile acid diarrhoea (BAD) is debilitating yet treatable, but it remains underdiagnosed due to challenging diagnostics. We developed a blood test-based method to guide BAD diagnosis. Design: We included serum from 50 treatment-naive patients with BAD diagnosed by gold standard 75selenium h...

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Detalhes bibliográficos
Autores: Lewinska, Monika, Kårhus, Martin Lund, Ellegaard, Anne-Marie Gade, Romero Gómez, Manuel, Macias, Rocio I R, Andersen, Jesper B., Knop, Filip Krag
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/144781
Acesso em linha:https://hdl.handle.net/11441/144781
https://doi.org/10.1136/gutjnl-2022-329213
Access Level:acceso abierto
Palavra-chave:Bile acid
Diarrhoea
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spelling Serum lipidome unravels a diagnostic potential in bile acid diarrhoeaLewinska, MonikaKårhus, Martin LundEllegaard, Anne-Marie GadeRomero Gómez, ManuelMacias, Rocio I RAndersen, Jesper B.Knop, Filip KragBile acidDiarrhoeaObjective: Bile acid diarrhoea (BAD) is debilitating yet treatable, but it remains underdiagnosed due to challenging diagnostics. We developed a blood test-based method to guide BAD diagnosis. Design: We included serum from 50 treatment-naive patients with BAD diagnosed by gold standard 75selenium homotaurocholic acid test, 56 feature-matched controls and 37 patients with non-alcoholic fatty liver disease (NAFLD). Metabolomes were generated using mass spectrometry covering 1295 metabolites and compared between groups. Machine learning was used to develop a BAD Diagnostic Score (BDS). Results: Metabolomes of patients with BAD significantly differed from controls and NAFLD. We detected 70 metabolites with a discriminatory performance in the discovery set with an area under receiver-operating curve metric above 0.80. Logistic regression modelling using concentrations of decanoylcarnitine, cholesterol ester (22:5), eicosatrienoic acid, L-alpha-lysophosphatidylinositol (18:0) and phosphatidylethanolamine (O-16:0/18:1) distinguished BAD from controls with a sensitivity of 0.78 (95% CI 0.64 to 0.89) and a specificity of 0.93 (95% CI 0.83 to 0.98). The model was independent of covariates (age, sex, body mass index) and distinguished BAD from NAFLD irrespective of fibrosis stage. BDS outperformed other blood test-based tests (7-alpha-hydroxy-4-cholesten-3-one and fibroblast growth factor 19) currently under development. Conclusions: BDS derived from serum metabolites in a single-blood sample showed robust identification of patients with BAD with superior specificity and sensitivity compared with current blood test-based diagnostics.Medicina2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/144781https://doi.org/10.1136/gutjnl-2022-329213reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésGut, 1-11.https://gut.bmj.com/content/early/2023/04/18/gutjnl-2022-329213info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1447812026-06-17T12:51:07Z
dc.title.none.fl_str_mv Serum lipidome unravels a diagnostic potential in bile acid diarrhoea
title Serum lipidome unravels a diagnostic potential in bile acid diarrhoea
spellingShingle Serum lipidome unravels a diagnostic potential in bile acid diarrhoea
Lewinska, Monika
Bile acid
Diarrhoea
title_short Serum lipidome unravels a diagnostic potential in bile acid diarrhoea
title_full Serum lipidome unravels a diagnostic potential in bile acid diarrhoea
title_fullStr Serum lipidome unravels a diagnostic potential in bile acid diarrhoea
title_full_unstemmed Serum lipidome unravels a diagnostic potential in bile acid diarrhoea
title_sort Serum lipidome unravels a diagnostic potential in bile acid diarrhoea
dc.creator.none.fl_str_mv Lewinska, Monika
Kårhus, Martin Lund
Ellegaard, Anne-Marie Gade
Romero Gómez, Manuel
Macias, Rocio I R
Andersen, Jesper B.
Knop, Filip Krag
author Lewinska, Monika
author_facet Lewinska, Monika
Kårhus, Martin Lund
Ellegaard, Anne-Marie Gade
Romero Gómez, Manuel
Macias, Rocio I R
Andersen, Jesper B.
Knop, Filip Krag
author_role author
author2 Kårhus, Martin Lund
Ellegaard, Anne-Marie Gade
Romero Gómez, Manuel
Macias, Rocio I R
Andersen, Jesper B.
Knop, Filip Krag
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Medicina
dc.subject.none.fl_str_mv Bile acid
Diarrhoea
topic Bile acid
Diarrhoea
description Objective: Bile acid diarrhoea (BAD) is debilitating yet treatable, but it remains underdiagnosed due to challenging diagnostics. We developed a blood test-based method to guide BAD diagnosis. Design: We included serum from 50 treatment-naive patients with BAD diagnosed by gold standard 75selenium homotaurocholic acid test, 56 feature-matched controls and 37 patients with non-alcoholic fatty liver disease (NAFLD). Metabolomes were generated using mass spectrometry covering 1295 metabolites and compared between groups. Machine learning was used to develop a BAD Diagnostic Score (BDS). Results: Metabolomes of patients with BAD significantly differed from controls and NAFLD. We detected 70 metabolites with a discriminatory performance in the discovery set with an area under receiver-operating curve metric above 0.80. Logistic regression modelling using concentrations of decanoylcarnitine, cholesterol ester (22:5), eicosatrienoic acid, L-alpha-lysophosphatidylinositol (18:0) and phosphatidylethanolamine (O-16:0/18:1) distinguished BAD from controls with a sensitivity of 0.78 (95% CI 0.64 to 0.89) and a specificity of 0.93 (95% CI 0.83 to 0.98). The model was independent of covariates (age, sex, body mass index) and distinguished BAD from NAFLD irrespective of fibrosis stage. BDS outperformed other blood test-based tests (7-alpha-hydroxy-4-cholesten-3-one and fibroblast growth factor 19) currently under development. Conclusions: BDS derived from serum metabolites in a single-blood sample showed robust identification of patients with BAD with superior specificity and sensitivity compared with current blood test-based diagnostics.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/144781
https://doi.org/10.1136/gutjnl-2022-329213
url https://hdl.handle.net/11441/144781
https://doi.org/10.1136/gutjnl-2022-329213
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Gut, 1-11.
https://gut.bmj.com/content/early/2023/04/18/gutjnl-2022-329213
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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