Titre :

Faecal proteomics links neutrophil degranulation with mortality in patients with alcohol-associated hepatitis.

Auteur(s) :

Kreimeyer, H. [Auteur]
Gonzalez, C. G. [Auteur]
Fondevila, M. F. [Auteur]
Hsu, C. L. [Auteur]
Hartmann, P. [Auteur]
Zhang, X. [Auteur]
Stärkel, P. [Auteur]
Bosques-Padilla, F. [Auteur]
Verna, E. C. [Auteur]
Abraldes, J. G. [Auteur]
Brown, R. S. [Auteur]
Vargas, V. [Auteur]
Altamirano, J. [Auteur]
Caballería, J. [Auteur]
Shawcross, D. L. [Auteur]
Louvet, Alexandre [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Lucey, M. R. [Auteur]
Mathurin, P. [Auteur]
Garcia-Tsao, G. [Auteur]
Bataller, R. [Auteur]
Investigators, A. [Auteur]
Gonzalez, D. J. [Auteur]
Schnabl, Bernd [Auteur]
University of California [San Diego] [UC San Diego]

Titre de la revue :

Gut

Nom court de la revue :

Gut

Éditeur :

BMJ Journals

Date de publication :

2024-07-22

ISSN :

1468-3288

Mot(s)-clé(s) en anglais :

ALCOHOLIC LIVER DISEASE
ALCOHOL-INDUCED INJURY

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Objective Patients with alcohol-associated hepatitis (AH) have a high mortality. Alcohol exacerbates liver damage by inducing gut dysbiosis, bacterial translocation and inflammation, which is characterised by increased ...
Lire la suite >Objective Patients with alcohol-associated hepatitis (AH) have a high mortality. Alcohol exacerbates liver damage by inducing gut dysbiosis, bacterial translocation and inflammation, which is characterised by increased numbers of circulating and hepatic neutrophils. Design In this study, we performed tandem mass tag (TMT) proteomics to analyse proteins in the faeces of controls (n=19), patients with alcohol-use disorder (AUD; n=20) and AH (n=80) from a multicentre cohort (InTeam). To identify protein groups that are disproportionately represented, we conducted over-representation analysis using Reactome pathway analysis and Gene Ontology to determine the proteins with the most significant impact. A faecal biomarker and its prognostic effect were validated by ELISA in faecal samples from patients with AH (n=70), who were recruited in a second and independent multicentre cohort (AlcHepNet). Result Faecal proteomic profiles were overall significantly different between controls, patients with AUD and AH (principal component analysis p=0.001, dissimilarity index calculated by the method of Bray-Curtis). Proteins that showed notable differences across all three groups and displayed a progressive increase in accordance with the severity of alcohol-associated liver disease were predominantly those located in neutrophil granules. Over-representation and Reactome analyses confirmed that differentially regulated proteins are part of granules in neutrophils and the neutrophil degranulation pathway. Myeloperoxidase (MPO), the marker protein of neutrophil granules, correlates with disease severity and predicts 60-day mortality. Using an independent validation cohort, we confirmed that faecal MPO levels can predict short-term survival at 60 days. Conclusions We found an increased abundance of faecal proteins linked to neutrophil degranulation in patients with AH, which is predictive of short-term survival and could serve as a prognostic non-invasive marker.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Date de dépôt :

2025-01-01T22:06:27Z
2025-01-15T08:32:26Z