Host transcriptome signatures in human faecal-washes predict histological remission in patients with IBD.

BACKGROUND

Colonoscopy is the gold standard for evaluation of inflammation in inflammatory bowel diseases (IBDs), yet entails cumbersome preparations and risks of injury. Existing non-invasive prognostic tools are limited in their diagnostic power. Moreover, transcriptomics of colonic biopsies have been inconclusive in their association with clinical features.

AIMS

To assess the utility of host transcriptomics of faecal wash samples of patients with IBD compared with controls.

METHODS

In this prospective cohort study, we obtained biopsies and faecal-wash samples from patients with IBD and controls undergoing lower endoscopy. We performed RNAseq of biopsies and matching faecal-washes, and associated them with endoscopic and histological inflammation status. We also performed faecal mass-spectrometry proteomics on a subset of samples. We inferred cell compositions using computational deconvolution and used classification algorithms to identify informative genes.

RESULTS

We analysed biopsies and faecal washes from 39 patients (20 IBD, 19 controls). Host faecal-transcriptome carried information that was distinct from biopsy RNAseq and faecal proteomics. Transcriptomics of faecal washes, yet not of biopsies, from patients with histological inflammation were significantly correlated to one another (p=5.3×10

CONCLUSIONS

Faecal wash host transcriptome is a statistically powerful biomarker reflecting histological inflammation. Furthermore, it opens the way to identifying important correlates and therapeutic targets that may be obscured using biopsy transcriptomics.

Informations de copyright

© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: SB-H received consulting and advisoryboard fees and/or research support from AbbVie, MSD, Janssen, Takeda andCellTrion. UK received speaker and advisory fees from: Abbvie, Jannsen, Gilead, MSD, Medtronic, Takeda and research support from: Jannsen, Medtronic, Takeda. RE received consultant and speaker fees from Janssen, Abbvie, Takeda and Medtronic. BU received consultation fees from Neopharm, Takeda, Janssen and Abbvie. DS received research support from Takeda and consultation and lecturing fees from AbbVie.