Microbial associations with disease activity at adult IBD onset

Introduction

Data on the microbiome profile of adult patients with IBD at inception, prior to treatment initiation, are sparse. Here we present data on the gut microbiome in new IBD at baseline with respect to clinical disease activity scores and Faecal Calprotectin (FCAL). We have previously shown that these patients have lower diversity and multiple taxa level differences compared to healthy controls.

Methods

Stool collected in DNA Genotek OM-200 kits was brought to the first pre-diagnosis outpatient review, alongside a sample for FCAL. Harvey Bradshaw Index (HBI), SESCD, Partial and endoscopic Mayo scores were collected at diagnosis before treatment. Stool microbial DNA was extracted with subsequent 16S rRNA PCR and sequencing. Diversity analysis and taxonomic classifications were performed in line with the QIIME2 workflow. Taxa associations were determined utilising the MaAsLin2 package and Kendall’s Tau coefficient.

Results

To date, faecal samples from 100 patients subsequently diagnosed with IBD (56 Crohn’s Disease [CD], 44 Ulcerative Colitis [UC]) have been sequenced. Median age was 35 and median FCAL 1181ug/g (IQR 1538). 21 had received antibiotics in the preceding 12 months. Amongst CD, median baseline HBI was 8 and SESCD 6.5, whilst in UC partial mayo was 4 and endoscopic mayo 2. In the IBD cohort higher relative abundance of taxa from the Fusobacteraeceae family showed the strongest association with increased FCAL. Increases in multiple Firmicutes including Gemellaceae and Peptostreptococcus Tissierellales families also associated with increased FCAL. Higher abundance of Verrucomicrobiota associated with lower FCAL. Increased abundance of Eubacterium Coprostanoligenes was associated with both lower HBI (CD) and Partial Mayo (UC). In UC, increases in multiple other taxa associated with reductions in partial mayo score, including the Ruminococcaceae, Oscilospiraceae and Bifidobacteriaceae. Increases in several Pasteurellaceae and Enterobacteriaceae correlated with increases in Partial Mayo. In CD, increased abundance of Eubacterium Eligens correlated with reduction in both HBI and SESCD, with other Lachnospiraceae including Roseburia, Agathobacter and Lachnospira associated with reduced SESCD. Higher abundances of Enterobacteriaceae were also seen to correlate with increased SESCD score. Key correlations are displayed in figure 1.

Conclusions

In this study of IBD patients before treatment we show key taxa (short chain fatty acid producers) associate with milder disease and key taxa link with FCAL. This suggests that the gut microbiome at baseline represents a novel ‘biomarker’ for disease as well as a target for specific intervention.