Imperial College London
Alternate

ProfessorJulianWalters

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Gastroenterology
 
 
 
//

Contact

 

+44 (0)20 3313 2361julian.walters

 
 
//

Location

 

Rm368, Hammersmith HouseHammersmith HospitalHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Quraishi:2020:ecco-jcc/jjaa021,
author = {Quraishi, MN and Acharjee, A and Beggs, AD and Horniblow, R and Tselepis, C and Gkoutus, G and Ghosh, S and Rossiter, A and Loman, N and van, Schaik W and Withers, D and Walters, JRF and Hirschfield, GM and Iqbal, TH},
doi = {ecco-jcc/jjaa021},
journal = {Journal of Crohns & Colitis},
pages = {935--947},
title = {A pilot integrative analysis of colonic gene expression, gut microbiota and immune infiltration in primary sclerosing cholangitis-inflammatory bowel disease: association of disease with bile acid pathways},
url = {http://dx.doi.org/10.1093/ecco-jcc/jjaa021},
volume = {14},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Although majority of patients with PSC have colitis (PSC-IBD) this is phenotypically different from UC. We sought to define further the pathophysiologic differences in PSC-IBD and UC, by applying a comparative and integrative approach in this pilot study. METHODS: Colonic biopsies were collected from patients with PSC-IBD (n=10), UC (n=10) and healthy controls (HC; n=10). Shotgun RNA-sequencing for differentially expressed colonic mucosal genes (DEGs), 16S rRNA analysis for microbial profiling and immunophenotyping were performed followed by multi-omic integration. RESULTS: The colonic transcriptome differed significantly between groups (P=0.01). Colonic transcriptomes from HC were different from both UC (1343 DEGs) and PSC-IBD (4312 DEGs). Of these genes, only 939 had shared differential gene expression in both UC and PSC-IBD compared to HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defence in both disease cohorts compared to HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared to UC (P=0.02). Microbiota profiles were different between the three groups (P=0.01); with inferred function in PSC-IBD also being consistent with dysregulation of bile acid metabolism. Th17 cells and IL17 producing CD4 cells were increased in both PSC-IBD and UC when compared to HC (P<0.05). Multi-omic integration revealed networks involved in bile acid homeostasis and cancer regulation in PSC-IBD. CONCLUSIONS: Colonic transcriptomic and microbiota analysis in PSC-IBD points toward dysregulation of colonic bile acid homeostasis compared to UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD.
AU  - Quraishi,MN
AU  - Acharjee,A
AU  - Beggs,AD
AU  - Horniblow,R
AU  - Tselepis,C
AU  - Gkoutus,G
AU  - Ghosh,S
AU  - Rossiter,A
AU  - Loman,N
AU  - van,Schaik W
AU  - Withers,D
AU  - Walters,JRF
AU  - Hirschfield,GM
AU  - Iqbal,TH
DO  - ecco-jcc/jjaa021
EP  - 947
PY  - 2020///
SN  - 1873-9946
SP  - 935
TI  - A pilot integrative analysis of colonic gene expression, gut microbiota and immune infiltration in primary sclerosing cholangitis-inflammatory bowel disease: association of disease with bile acid pathways
T2  - Journal of Crohns & Colitis
UR  - http://dx.doi.org/10.1093/ecco-jcc/jjaa021
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32016358
UR  - http://hdl.handle.net/10044/1/86489
VL  - 14
ER  -
Download