Colonic Gene Expression and Fecal Microbiota in Diarrhea-predominant Irritable Bowel Syndrome : Increased Toll-like Receptor 4 but Minimal Inflammation and no Response to Mesalazine

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Jalanka , J , Lam , C , Bennett , A , Hartikainen , A , Crispie , F , Finnegan , L A , Cotter , P D & Spiller , R 2021 , ' Colonic Gene Expression and Fecal Microbiota in Diarrhea-predominant Irritable Bowel Syndrome : Increased Toll-like Receptor 4 but Minimal Inflammation and no Response to Mesalazine ' , Journal of neurogastroenterology and motility , vol. 27 , no. 2 , pp. 279-291 . https://doi.org/10.5056/jnm20205

Title: Colonic Gene Expression and Fecal Microbiota in Diarrhea-predominant Irritable Bowel Syndrome : Increased Toll-like Receptor 4 but Minimal Inflammation and no Response to Mesalazine
Author: Jalanka, Jonna; Lam, Ching; Bennett, Andrew; Hartikainen, Anna; Crispie, Fiona; Finnegan, Laura A.; Cotter, Paul D.; Spiller, Robin
Other contributor: University of Helsinki, TRIMM - Translational Immunology Research Program
University of Helsinki, HUMI - Human Microbiome Research




Date: 2021-04
Language: eng
Number of pages: 13
Belongs to series: Journal of neurogastroenterology and motility
ISSN: 2093-0879
DOI: https://doi.org/10.5056/jnm20205
URI: http://hdl.handle.net/10138/331753
Abstract: Background/Aims Diarrhea-predominant irritable bowel syndrome (IBS-D) has been previously associated with evidence of immune activation and altered microbiota. Our aim is to assess the effect of the anti-inflammatory agent, mesalazine, on inflammatory gene expression and microbiota composition in IBS-D. Methods We studied a subset of patients (n = 43) from a previously published 12-week radomized placebo-controlled trial of mesalazine. Mucosal biopsies were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction for a range of markers of inflammation, altered permeability, and sensory receptors including Toll-like receptors (TLRs) at randomization after treatment. All biopsy data were compared to 21 healthy controls. Patient's stool microbiota composition was analysed through 16S ribosomal RNA sequencing. Results We found no evidence of increased immune activation compared to healthy controls. However, we did find increased expression of receptors in both sensory pathways and innate immune response including TLR4. Higher TLR4 expression was associated with greater urgency. TLR4 expression correlated strongly with the expression of the receptors bradykinin receptor B2, chemerin chemokine-like receptor 1, and transient receptor potential cation channel, subfamily A, member 1 as well as TLR4's downstream adaptor myeloid differentiation factor 88. Mesalazine had minimal effect on either gene expression or microbiota composition. Conclusions Biopsies from a well-characterized IBS-D cohort showed no substantial inflammation. Mesalazine has little effect on gene expression and its previous reported effect on fecal microbiota associated with much greater inflammation found in inflammatory bowel diseases is likely secondary to reduced inflammation. Increased expression of TLR4 and correlated receptors in IBS may mediate a general increase in sensitivity to external stimuli, particularly those that signal via the TLR system.
Subject: Gene expression
Irritable bowel syndrome
Mesalazine
Microbiota
Toll-like receptor 4
5-AMINOSALICYLIC ACID
GASTROINTESTINAL MOTILITY
PROTEASE ACTIVITY
GUT MICROBIOTA
IBS
PERMEABILITY
ACTIVATION
BRADYKININ
BACTERIAL
SEVERITY
3121 General medicine, internal medicine and other clinical medicine
3112 Neurosciences
3124 Neurology and psychiatry
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