Impact of Antibiotic Resistance Genes in Gut Microbiome of Patients With Cirrhosis

Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved..

BACKGROUND AND AIMS: Cirrhosis is associated with changes in intestinal microbiota that can lead to hepatic encephalopathy (HE) and infections, especially with antibiotic-resistant organisms. However, the impact of gut microbial antibiotic resistance gene (ARG) burden on clinical outcomes is unclear. The aims of the study were to determine the impact of ARGs in cirrhosis-related gut metagenome on outcomes and disease progression, study the effect of rifaximin on ARG burden, and compare ARGs in cirrhosis with chronic kidney disease (CKD) and diabetes.

METHODS: In outpatients with cirrhosis who underwent metagenomics, we evaluated change in ARG abundances with progression and their multivariable impact on 90-day hospitalizations and deaths over 1 year. We also studied ARGs pre- and 8 weeks post-rifaximin in patients with compensated cirrhosis in an open-label trial. Finally, ARGs from CKD and diabetes studies were compared with cirrhosis on machine learning.

RESULTS: A total of 163 patients with cirrhosis (43 compensated, 20 ascites-only, 30 HE-only, 70 both) and 40 controls were included. ARG abundances were higher in cirrhosis versus controls and worsened with advancing cirrhosis severity; 44 patients were hospitalized and 14 died. ARG abundances were associated with hospitalizations and mortality while controlling for cirrhosis complications, medications, and demographics. Rifaximin trial: ARG abundance patterns were minimally affected in 19 patients post-rifaximin. CKD/diabetes comparison: ARG abundance patterns in cirrhosis are distinguishable on machine learning and include more gram-positive ARGs.

CONCLUSIONS: Cirrhosis is associated with high gut microbial ARG gene burden compared with controls, which worsens with disease progression and may be different from CKD and diabetes. ARGs are not affected by rifaximin and are associated with hospitalizations and death.

Errataetall:

CommentIn: Gastroenterology. 2021 Aug;161(2):413-415. - PMID 34048780

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:161

Enthalten in:

Gastroenterology - 161(2021), 2 vom: 08. Aug., Seite 508-521.e7

Sprache:

Englisch

Beteiligte Personen:

Shamsaddini, Amirhossein [VerfasserIn]
Gillevet, Patrick M [VerfasserIn]
Acharya, Chathur [VerfasserIn]
Fagan, Andrew [VerfasserIn]
Gavis, Edith [VerfasserIn]
Sikaroodi, Masoumeh [VerfasserIn]
McGeorge, Sara [VerfasserIn]
Khoruts, Alexander [VerfasserIn]
Albhaisi, Somaya [VerfasserIn]
Fuchs, Michael [VerfasserIn]
Sterling, Richard K [VerfasserIn]
Bajaj, Jasmohan S [VerfasserIn]

Links:

Volltext

Themen:

Anti-Bacterial Agents
Ascites
Hepatic Encephalopathy
Infections
Journal Article
L36O5T016N
Machine Learning
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Rifaximin

Anmerkungen:

Date Completed 18.01.2022

Date Revised 02.08.2022

published: Print-Electronic

CommentIn: Gastroenterology. 2021 Aug;161(2):413-415. - PMID 34048780

Citation Status MEDLINE

doi:

10.1053/j.gastro.2021.04.013

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM324122160