Multiomic Study Investigates Mucosal Healing in Pediatric Crohn Disease

The goal of this study was to describe changes in the microbiota, metabolome, and protease activity related to mucosal healing in established pediatric Crohn disease.

Study data published in Alimentary Pharmacology & Therapeutics describe changes in the microbiota that accompany mucosal healing in established pediatric Crohn disease (CD). Patients with mucosal healing — defined by low fecal calprotectin levels — displayed greater abundance of Dialister species, higher concentrations of pentanoate, and lower concentrations of lysine compared with patients with higher calprotectin levels.

Treatment of pediatric CD suppresses mucosal inflammation, with an aim to induce “mucosal healing.” Investigators sought to characterize microbial changes in patients who achieve mucosal healing with CD treatment. This multicenter clinical cohort study recruited children with CD from clinical centers in North West London. All participants had a confirmed diagnosis of pediatric CD with a duration greater than 6 months. All were receiving maintenance biological therapy with infliximab, adalimumab, or vedolizumab beyond the induction phase.

Participants provided a sample of whole stool for microbiome, metabolome, and protease activity analysis. Investigators used fecal calprotectin as a marker of mucosal healing. They classified participants into 2 groups: (1) mucosal healing (fecal calprotectin <100 μg/g) and (2) no mucosal healing (fecal calprotectin ≥100 μg/g). Researchers performed 16S gene-based metataxonomic analysis to identify microorganisms in the gut. They characterized metabolites in fecal samples using 1-hydrogen nuclear magnetic resonance (1H-NMR) spectroscopy and also performed protease activity assays.

The study cohort comprised 25 patients aged 3 to 18 years with pediatric CD. Data on calprotectin levels were available for 22 participants, among whom 11 had high levels and 11 had low levels. Bacterial diversity and community composition were similar between groups; however, relative abundance of Dialister species increased 6-fold in the low vs high calprotectin group (q =.00999). Dialister was significantly negatively correlated with calprotectin levels (P =.0001).

Alpha and beta diversity and total protease activity did not differ between the calprotectin groups; however, per 1H-NMR-based metabolic profiling, the mean concentration of pentanoate was 1.35 times greater in the low calprotectin group vs high calprotectin group (95% CI, 1.03-1.68; P =.036). The relative concentration of lysine was 1.54 times greater in the high-calprotectin group compared with the low-calprotectin group (95% CI, 1.05-2.03; P = .028).

This study identified multiomic features of mucosal healing in pediatric CD, including an increase in Dialister species abundance, greater pentanoate concentration, and lower lysine concentration.

The primary study limitations were its cross-sectional design and small cohort. Longitudinal analysis of a larger dataset could allow for further insight into the process of mucosal healing.

Disclosure: Two study authors declared affiliations with the pharmaceutical industry.

Please see the original reference for a full list of authors’ disclosures.


Taylor H, Serrano-Contreras JI, McDonald JAK, et al. Multiomic features associated with mucosal healing and inflammation in paediatric Crohn’s disease. Aliment Pharmacol Ther. 2020;52(9):1491-1502.