Metabonomics and the Gut Microbiome Associated With Primary Response to Anti-TNF Therapy in Crohn's Disease.
Adalimumab
/ administration & dosage
Adult
Bile Acids and Salts
/ analysis
Biomarkers, Pharmacological
/ analysis
Crohn Disease
/ diagnosis
Cysteine
/ analysis
Feces
Female
Histidine
/ analysis
Humans
Inflammation
/ blood
Infliximab
/ administration & dosage
Lipid Metabolism
/ drug effects
London
Longitudinal Studies
Male
Metabolomics
/ methods
Predictive Value of Tests
RNA, Ribosomal, 16S
/ analysis
Tumor Necrosis Factor Inhibitors
/ administration & dosage
Crohn’s disease
metabolomics
microbiota
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
07 Sep 2020
07 Sep 2020
Historique:
pubmed:
3
3
2020
medline:
15
7
2021
entrez:
3
3
2020
Statut:
ppublish
Résumé
Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn's disease. Patients with luminal Crohn's disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces. Samples were collected from 76 Crohn's disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn's patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn's disease. This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn's disease. This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn's disease.
METHODS
METHODS
Patients with luminal Crohn's disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces.
RESULTS
RESULTS
Samples were collected from 76 Crohn's disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn's patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn's disease.
CONCLUSIONS
CONCLUSIONS
This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn's disease.
PODCAST
UNASSIGNED
This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.
Identifiants
pubmed: 32119090
pii: 5771407
doi: 10.1093/ecco-jcc/jjaa039
doi:
Substances chimiques
Bile Acids and Salts
0
Biomarkers, Pharmacological
0
RNA, Ribosomal, 16S
0
Tumor Necrosis Factor Inhibitors
0
Histidine
4QD397987E
Infliximab
B72HH48FLU
Adalimumab
FYS6T7F842
Cysteine
K848JZ4886
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1090-1102Subventions
Organisme : Medical Research Council
ID : MR/P028225/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.