Mucosal and Plasma Metabolomes in New-onset Paediatric Inflammatory Bowel Disease: Correlations with Disease Characteristics and Plasma Inflammation Protein Markers

Abstract

Background and Aims To advance the understanding of inflammatory bowel disease (IBD) pathophysiology, we compared the mucosal and plasma metabolomes between new-onset paediatric IBD patients and symptomatic non-IBD controls, and correlated plasma inflammation markers and disease characteristics with the altered metabolites. Methods Paired colonic and ileal biopsies and plasma from 67 treatment-naïve children with incident Crohn’s disease (CD; n=47), ulcerative colitis (UC; n=9), and non-IBD controls (n=11) were analysed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Inflammatory plasma proteins (n=92) were assessed. Results The metabolomes in inflamed mucosal biopsies differed between IBD patients and controls. In CD, mucosal levels of several lysophospholipids (lysophosphatidylcholines, lysophosphatidyletanolamines, lysophosphatidylinositols, and lysophosphatidylserines) were decreased, correlating with various plasma metabolites, including amino acid analogues and N-acetylated compounds. In both CD and UC, mucosal sphingolipids, including ceramide (d18:2/24:1, d18:1/24:2), lactosyl-N-palmitoyl-sphingosine (d18:1/16:0), behenoyl sphingomyelin (d18:1/22:0), lignoceroyl sphingomyelin (d18:1/24:0), and/or sphingomyelin (d18:1/24:1, d18:2/24:0) were increased, correlating with sphingolipids, bile acids, and/or N-acetylated metabolites in plasma. Among proteins associated with CD, interleukin-24 correlated with plasma metabolites, including lactosyl-N-palmitoyl sphingosine (d18:1/16:0) and phosphatidyletanolamine (18:1/18:1), haemoglobin, and faecal calprotectin. In UC, interleukin-24, interleukin-17A, and C-C motif chemokine 11 correlated with several plasma metabolites, including N-acetyltryptophan, tryptophan, glycerate, and threonate, and with the paediatric ulcerative colitis activity index, C-reactive protein, and faecal-calprotectin. Conclusions Mucosal perturbations of lysophospholipids and sphingolipids characterised the metabolome in new-onset paediatric IBD and correlated with plasma metabolites. By integrating plasma metabolomics data with inflammatory proteins and clinical data, we identified clinical and inflammatory markers associated with metabolomic signatures for IBD.

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“…Paine A et al showed that Glycoursodeoxycholic acid sulfate (1) levels are sensitive and speci c predictors of progression from Psoriasis (Ps) to Psoriatic Arthritis (PsA) [34] . Nystrom N et al showed that Behenoyl sphingomyelin (d18:1/22:0) levels are involved in the in ammatory response and are increased in neonatal in ammatory bowel disease [35] . Per uorooctane sulfonate (PFOS) levels are a toxic and carcinogenic persistent organic pollutant to the human body that induces apoptosis of immune cells, destroys the immune system, and ultimately leads to cancer and toxic damage [36] .…”

Identifying Robust Biomarkers for the Diagnosis and Subtype Distinction of Inflammatory Bowel Disease through Comprehensive Serum Metabolomic Profiling

“…[38] We anticipate that subsequent studies will delve into the complex connections between serum metabolites, gut microbiota, and their metabolites, further insights as recently explored in the context of mucosal and plasma metabolomes, and their correlation with disease characteristics in pediatric IBD. [39] Finally, in this study, we did not exactly match patients with IBD to normal controls because the control subjects were healthy volunteers. Consequently, we adjusted for age, sex, and BMI in our multivariate analysis to account for these differences.…”

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