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DOP08 Deep remission in paediatric Crohn’s disease is associated with increased abundance of dialister species and increased valerate

H. Taylor1, J. McDonald1, J.I. Serrano Contreras1, J. Li1, J. Marchesi1, A. Hart1,2

1Department of Medicine, Imperial College London, London, UK, 2Inflammatory Bowel Disease Unit, St Mark’s Academic Institute, London, UK

Background

Deep remission, or the absence of mucosal inflammation on endoscopy, is associated with improved long-term outcomes in paediatric Crohn’s disease (pCD). In pCD faecal calprotectin level <100 mg/l is a validated non-invasive marker of deep remission and is a therapeutic target used in clinical practice. The microbiome in pCD has been extensively compared with controls and is known to have reduced diversity, high instability, and depleted short-chain fatty acid (SCFA) producers. This study investigates variation in microbiome, metabolome and protease activity associated with deep remission.

Methods

Children aged 3–18 years with established pCD on infliximab were recruited. Stool samples were cooled immediately, aliquoted, and frozen at −80oC within 4 h. Deep remission status was assigned if the calprotectin level was under 100 mg/l. 16S sequencing and analysis used Illumina MiSeq (V1-2 primers), DADA2, and STAMP. ¹H-NMR spectral profiles were used to develop partial-least-squares discriminant-analysis with Monte-Carlo cross-validation (MCCV-PLS-DA) models. Metabolome microbiome correlation used Storey’s method for multiple testing correction and a threshold of │RHO│≥ 0.5 with q < 0.05. Protease activity was assayed by comparing the breakdown of fluorescein labelled casein against trypsin standards.

Results

Twenty-one children were included; 10 were in deep remission and 11 had active disease. There were no significant differences in age, disease duration, treatment, or BMI between groups. Mean height z score was lower in those with active disease (p = 0.015). There was no significant difference in α diversity between groups, and non-metric multidimensional scaling of weighted unifrac distance identified no difference in community composition (PERMANOVA p = 0.317). The relative abundance of Dialister species was higher in those with deep remission (3.4 vs. 0.4%, q = 0.033). Dialister abundance was positively correlated with valerate concentration. MCCV–PLS-DA was able to effectively discriminate metabolome profiles from active and deep remission patients (R2 = 0.87, Q2 = 0.51); valerate and glutamate were increased in deep remission, ethanol and lysine were decreased. There was a trend towards increased protease activity in patients with active disease (p = 0.054).

Conclusion

Dialister species are enriched in pCD in deep remission and are associated with significant metabolome changes, including increased valerate. Valerate, like other SCFAs, has known anti-inflammatory properties and has previously been implicated in effective C. difficile treatment. This study supports an association between Dialister abundance, valerate and mucosal healing in pCD. A trend towards higher protease activity in active disease also warrants further investigation.

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