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In Alimentary pharmacology & therapeutics ; h5-index 83.0

BACKGROUND : The gastrointestinal microbiota has an important role in mucosal immune homoeostasis and may contribute to maintaining mucosal healing in Crohn's disease (CD).

AIM : To identify changes in the microbiota, metabolome and protease activity associated with mucosal healing in established paediatric CD.

METHODS : Twenty-five participants aged 3-18 years with CD, disease duration of over 6 months, and maintenance treatment with biological therapy were recruited. They were divided into a low calprotectin group (faecal calprotectin <100 μg/g, "mucosal healing," n = 11), and a high calprotectin group (faecal calprotectin >100 μg/g, "mucosal inflammation," n = 11). 16S gene-based metataxonomics, 1 H-NMR spectroscopy-based metabolic profiling and protease activity assays were performed on stool samples.

RESULTS : Relative abundance of Dialister species was six times greater in the low calprotectin group (q = 0.00999). Alpha and beta diversity, total protease activity and inferred metagenomic profiles did not differ between groups. Pentanoate (valerate) and lysine were principal discriminators in a machine-learning model which differentiated high and low calprotectin samples using NMR spectra (R2 0.87, Q2 0.41). Mean relative concentration of pentanoate was 1.35-times greater in the low calprotectin group (95% CI 1.03-1.68, P = 0.036) and was positively correlated with Dialister. Mean relative concentration of lysine was 1.54-times greater in the high calprotectin group (95% CI 1.05-2.03, P = 0.028).

CONCLUSIONS : This multiomic study identified an increase in Dialister species and pentanoate, and a decrease in lysine, in patients with "mucosal healing." It supports further investigation of these as potential novel therapeutic targets in CD.

Taylor Henry, Serrano-Contreras Jose Ivan, McDonald Julie A K, Epstein Jenny, Fell J M, Seoane Rocio C, Li Jia V, Marchesi Julian R, Hart Ailsa L

2020-Sep-14