Impact of Antibiotic Resistance Genes in Gut Microbiome of Patients With Cirrhosis.
Adult
Aged
Anti-Bacterial Agents
/ adverse effects
Bacteria
/ drug effects
Case-Control Studies
Cross-Sectional Studies
Disease Progression
Drug Resistance, Bacterial
/ genetics
Dysbiosis
Female
Gastrointestinal Microbiome
/ drug effects
Hospitalization
Humans
Intestines
/ microbiology
Liver Cirrhosis
/ diagnosis
Male
Metagenome
Metagenomics
Middle Aged
Rifaximin
/ adverse effects
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome
Young Adult
Ascites
Hepatic Encephalopathy
Infections
Machine Learning
Rifaximin
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
12
01
2021
revised:
02
04
2021
accepted:
05
04
2021
pubmed:
16
4
2021
medline:
19
1
2022
entrez:
15
4
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 33857456
pii: S0016-5085(21)00634-X
doi: 10.1053/j.gastro.2021.04.013
pmc: PMC9069394
mid: NIHMS1693080
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Rifaximin
L36O5T016N
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
508-521.e7Subventions
Organisme : NCATS NIH HHS
ID : R21 TR003095
Pays : United States
Organisme : NCATS NIH HHS
ID : R21 TR002024
Pays : United States
Organisme : CSRD VA
ID : I01 CX000176
Pays : United States
Organisme : CSRD VA
ID : I01 CX001076
Pays : United States
Organisme : CSRD VA
ID : I01 CX001761
Pays : United States
Organisme : AHRQ HHS
ID : R01 HS025412
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.
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