eHealth: Disease activity measures are related to the faecal gut microbiota in adult patients with ulcerative colitis

Abstract

Background/Aim

Microbial dysbiosis in inflammatory bowel disease (IBD) is poorly understood. Faecal samples collected for the purposes of microbiota analysis are not yet a part of everyday clinical practice. To explore associations between faecal microbiota and disease activity measures in adult IBD patients, for the purpose of possibly integrating microbiota measures in an existing IBD eHealth application for disease-monitoring.

Methods

We collected faecal samples from adult IBD patients for one year while they were home-monitoring for disease activity, using faecal calprotectin (FC) and the Simple Clinical Colitis Activity Index (SCCAI). Faecal samples were analysed in two different ways: commercially available test consisting of 54 pre-determined bacterial markers (DNA test) and 16S rRNA gene sequencing (16S-seq). Univariable linear mixed effect models were fitted to predict disease scores using normalised relative abundances as fixed effects.

Results

Seventy-eight IBD patients provided a total of 288 faecal samples for microbiota analysis. Two hundred and thirty-four of the samples were from patients with ulcerative colitis (UC). Peptostreptococcus anaerobius was found to correlate significantly with increasing FC, while an additional 24 genera were found to be associated with FC and/or SCCAI (16S-seq). Bacterial markers (DNA test) for Proteobacteria, Shigella spp. and Escherichia spp., were significantly correlated with increasing FC measures, while another 14 markers were found to be associated with FC and/or SCCAI.

Conclusions

In patients with UC, results of both methods are associated with disease activity, correlating significantly with Peptostretococcus anaerobius (16S-seq) and with Proteobacteria, Shigella spp. and Escherichia spp. (DNA test).

Keywords:

• Inflammatory bowel disease
• ulcerative colitis
• disease activity
• faecal calprotectin
• microbiota

Disclosure statement

DVA has received grants from the Crohn’s & Colitis patient society, Denmark, North Zealand University Hospital, Ferring Pharmaceuticals and non-financial support from Calpro AS. PW has received consulting fees from Vifor Pharma Nordiska AB, grants from Ferring lægemidler and Tillotts Pharma AG, as well as non-financial support from Janssen-Cilag A/S, Calpro AS, Pharmacosmos A/S and Vifor Pharma Nordiska AB. DM has received non-financial support from Calpro AS and Pfizer. ABK is an employee at Genetic Analysis AS. KP is an employee of Ferring Pharmaceuticals. JB has received personal fees from AbbVie, Janssen-Cilag, Celgene, Samsung Biopies, MSD, Pfizer, and Coloplast, as well as grants and personal fees from Takeda and Tillots Pharma. PM has received financial, as well as non-financial, support from AstraZeneca, Pfizer, Janssen-Cilag, Tillotts Pharma, MSD, Ferring Pharmaceuticals and Calpro AS. The remaining authors have no interests to declare.

Author contributions

DVA prepared the manuscript, which was critically reviewed by all co-authors. DVA, DM, JB and PM designed the study. DM, PM, DVA conducted the study. DVA and TJ had full access to study data and take full responsibility for their integrity. TJ, ABK and BL carried out the bioinformatic analyses. All authors approved the final version of the manuscript. PM is the guarantor of the article.

Additional information

Funding

Grants supporting this study were provided by North Zealand University Hospital, Ferring Pharmaceuticals and Crohn’s & Colitis patient society Denmark. This study was also supported in part by Genetic Analysis AS, Calpro AS.