Systematic Review: The association between the gut microbiota and medical therapies in inflammatory bowel disease
File(s)APT-1242-2021.R1_Proof_hi.pdf (914.8 KB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Background
The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype.
Aims
To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota.
Methods
We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included.
Results
We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α-diversity was observed in responders versus non-responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post-treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti-TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate-treated patients.
Conclusions
Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments.
The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype.
Aims
To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota.
Methods
We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included.
Results
We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α-diversity was observed in responders versus non-responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post-treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti-TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate-treated patients.
Conclusions
Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments.
Date Issued
2022-01
Date Acceptance
2021-10-06
Citation
Alimentary Pharmacology and Therapeutics, 2022, 55 (1), pp.26-48
ISSN
0269-2813
Publisher
Wiley
Start Page
26
End Page
48
Journal / Book Title
Alimentary Pharmacology and Therapeutics
Volume
55
Issue
1
Copyright Statement
© 2021 John Wiley & Sons Ltd. This is the accepted version of the following article: Radhakrishnan, ST, Alexander, JL, Mullish, BH, et al. Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease. Aliment Pharmacol Ther. 2021; 00: 1– 23, which has been published in final form at https://doi.org/10.1111/apt.16656
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
https://onlinelibrary.wiley.com/doi/10.1111/apt.16656
Grant Number
RDA02
RDA27
Subjects
Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
Pharmacology & Pharmacy
PEDIATRIC CROHNS-DISEASE
ULCERATIVE-COLITIS
FECAL MICROBIOTA
METAANALYSES
PREVALENCE
METABOLISM
MODULATION
MANAGEMENT
REMISSION
DYSBIOSIS
Gastroenterology & Hepatology
1103 Clinical Sciences
1115 Pharmacology and Pharmaceutical Sciences
Publication Status
Published
Date Publish Online
2021-11-09