ABSTRACT
BACKGROUND AND AIMS: We aimed to identify serum metabolites associated with mucosal and transmural inflammation in pediatric Crohn disease (pCD). METHODS: Fifty-six pCD patients were included through a pre-planned sub-study of the multicenter, prospective, ImageKids cohort, designed to develop the Pediatric Inflammatory Crohn's MRE Index (PICMI). Children were included throughout their disease course when undergoing ileocolonoscopy and magnetic resonance enterography (MRE) and followed for 18 months when MRE was repeated. Serum metabolites were identified using liquid chromatography/mass spectroscopy. Outcomes included: PICMI, the simple endoscopic score (SES), faecal calprotectin (FCP), and C-reactive protein (CRP), to assess transmural, mucosal, and systemic inflammation, respectively. Random forest models were built by outcome. Maximum relevance minimum redundancy (mRMR) feature selection with a j-fold cross validation scheme identified the best subset of features and hyperparameter settings. RESULTS: Tryptophan and glutarylcarnitine were the top common mRMR metabolites linked to pCD inflammation. Random forest models established that amino acids and amines were among the most influential metabolites for predicting transmural and mucosal inflammation. Predictive models performed well, each with an area under the curve (AUC) > 70%. In addition, serum metabolites linked with pCD inflammation mainly related to perturbations in citrate cycle (TCA cycle), aminoacyl-tRNA biosynthesis, tryptophan metabolism, butanoate metabolism, and tyrosine metabolism. CONCLUSIONS: We extend on recent studies, observing differences in serum metabolite between healthy controls and Crohn disease patients, and suggest various associations of serum metabolites with transmural and mucosal inflammation. These metabolites could improve the understanding of pCD pathogenesis and assess disease severity.
ABSTRACT
To review and discuss recent findings on the associations between pediatric/early-life exposures to ambient air pollution and the risk of pediatric-onset inflammatory bowel diseases (IBD). A scoping review was conducted using the Peters Micah et al. framework. We searched, selected, extracted, and reviewed information from published peer-reviewed papers from three bibliographic databases, chosen to cover a broad range of disciplines. Limits on date (last decade), language, and subject were placed on the database search. The search identified 109 papers from 2010 to June 2021. After screening, we identified nine articles with data on air pollution as a risk factor for IBD, but only four epidemiologic studies directly investigated the association between air pollution and IBD development in children and young adults. These four papers show that air pollution components have different associations with pediatric IBD (pIBD) incidence. Consequently, sulfur dioxide (SO2), nitrogen dioxide (NO2), and the oxidant capacity of air pollution (Ox) were positively associated with pIBD incidence, whereas the association effects of particulate matter (PM) and ozone (O3) exposures were not clear. Despite good scientific rationale and some studies, the evidence on the role that air pollution has in IBD development is limited, highlighting the need for further investigation. Future studies should include the epidemiology of air pollutants and its sources, identifying and understanding mechanisms linking air pollution and pIBD, and identifying signatures of biological responses to air pollutants.
