Mucosal 5-aminosalicylic acid concentration, drug formulation and mucosal microbiome in patients with quiescent ulcerative colitis.
Adult
Anti-Inflammatory Agents, Non-Steroidal
/ pharmacokinetics
Arylamine N-Acetyltransferase
/ genetics
Colitis, Ulcerative
/ drug therapy
Drug Compounding
Feces
/ microbiology
Female
Humans
Intestinal Mucosa
/ metabolism
Isoenzymes
/ genetics
Male
Mesalamine
/ pharmacokinetics
Microbiota
/ drug effects
Middle Aged
Young Adult
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
04
12
2018
revised:
18
01
2019
accepted:
22
02
2019
pubmed:
22
3
2019
medline:
21
3
2020
entrez:
22
3
2019
Statut:
ppublish
Résumé
5-aminosalicylic acid (5-ASA) is the first-line therapy for ulcerative colitis (UC). 5-ASA acts locally in the colonic mucosa by numerous proposed mechanisms, and is metabolised by N-acetyltransferase (NAT). Large variations in mucosal 5-ASA concentrations have been reported, but the underlying mechanisms are not understood. To study the relationship between 5-ASA concentration, 5-ASA formulation, NAT genotype and bacterial microbiome in patients with UC. Patients with quiescent UC, using monotherapy of Mezavant (n = 18), Asacol (n = 14) or Pentasa (n = 10), 4.0-4.8 g/day were included. 5-ASA was measured in colonic mucosal biopsies and serum by ultra-high performance liquid chromatography. NAT genotypes were determined by Sanger sequencing. Bacterial microbiome was sequenced from faeces and mucosa by 16S rRNA sequencing using Illumina Miseq. Mezavant provided the highest mucosal 5-ASA levels (geometric mean 2.39 ng/mg), followed by Asacol (1.60 ng/mg, 33% lower, P = 0.50) and Pentasa (0.57 ng/mg, 76% lower, P = 0.033). Mucosal 5-ASA concentration was not associated with NAT genotype, but serum 5-ASA concentration and NAT1 genotype was associated (P = 0.044). Mucosal 5-ASA concentration was positively associated with mucosal bacterial diversity (P = 0.0005) and bacterial composition. High mucosal 5-ASA concentration was related to reduced abundance of pathogenic bacteria such as Proteobacteria, and increased abundance of several favourable bacteria such as Faecalibacterium. Mucosal 5-ASA concentration is positively associated with bacterial diversity and a mucosal bacterial composition that are perceived favourable in UC. Mezavant yielded higher mucosal 5-ASA concentrations than Pentasa. 5-ASA may have beneficial effects on the mucosal microbiome, and high concentrations possibly amend dysbiosis in UC.
Sections du résumé
BACKGROUND
5-aminosalicylic acid (5-ASA) is the first-line therapy for ulcerative colitis (UC). 5-ASA acts locally in the colonic mucosa by numerous proposed mechanisms, and is metabolised by N-acetyltransferase (NAT). Large variations in mucosal 5-ASA concentrations have been reported, but the underlying mechanisms are not understood.
AIM
To study the relationship between 5-ASA concentration, 5-ASA formulation, NAT genotype and bacterial microbiome in patients with UC.
METHODS
Patients with quiescent UC, using monotherapy of Mezavant (n = 18), Asacol (n = 14) or Pentasa (n = 10), 4.0-4.8 g/day were included. 5-ASA was measured in colonic mucosal biopsies and serum by ultra-high performance liquid chromatography. NAT genotypes were determined by Sanger sequencing. Bacterial microbiome was sequenced from faeces and mucosa by 16S rRNA sequencing using Illumina Miseq.
RESULTS
Mezavant provided the highest mucosal 5-ASA levels (geometric mean 2.39 ng/mg), followed by Asacol (1.60 ng/mg, 33% lower, P = 0.50) and Pentasa (0.57 ng/mg, 76% lower, P = 0.033). Mucosal 5-ASA concentration was not associated with NAT genotype, but serum 5-ASA concentration and NAT1 genotype was associated (P = 0.044). Mucosal 5-ASA concentration was positively associated with mucosal bacterial diversity (P = 0.0005) and bacterial composition. High mucosal 5-ASA concentration was related to reduced abundance of pathogenic bacteria such as Proteobacteria, and increased abundance of several favourable bacteria such as Faecalibacterium.
CONCLUSIONS
Mucosal 5-ASA concentration is positively associated with bacterial diversity and a mucosal bacterial composition that are perceived favourable in UC. Mezavant yielded higher mucosal 5-ASA concentrations than Pentasa. 5-ASA may have beneficial effects on the mucosal microbiome, and high concentrations possibly amend dysbiosis in UC.
Identifiants
pubmed: 30895635
doi: 10.1111/apt.15227
pmc: PMC6593792
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Isoenzymes
0
Mesalamine
4Q81I59GXC
Arylamine N-Acetyltransferase
EC 2.3.1.5
N-acetyltransferase 1
EC 2.3.1.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1301-1313Subventions
Organisme : Liaison Committee between Central Norway Regional Health Authority (RHA) and Norwegian University of Science and Technology (NTNU)
Pays : International
Organisme : St.Olav´s Hospital, Trondheim University Hospital
Pays : International
Organisme : Faculty of Medicine and Health Sciences at NTNU and RHA
Pays : International
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2019 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.
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