Metabolomic Signatures in Pediatric Crohn’s Disease Patients with Mild or Quiescent Disease Treated with Partial Enteral Nutrition: A Feasibility Study

Abstract

Little is known about the metabolic response of pediatric Crohn’s disease (CD) patients to partial enteral nutrition (PEN) therapy and the impact of disease activity and inflammation. We analyzed plasma samples from a nonrandomized controlled intervention study investigating the effect of partial enteral nutrition (PEN) on bone health and growth throughout one year with untargeted metabolomics using high-performance liquid chromatography (HPLC) coupled with high-resolution mass spectrometry (HRMS). Thirty-four paired samples from two time points (baseline and 12 months) were analyzed. Patients (median age: 13.9 years, range: 7–18.9 years, 44% females) were in remission or had mild disease activity. The intervention group received a casein-based formula for 12 months, providing ~25% of estimated daily energy requirements. Sparse partial least squares discriminant analysis (splsda) was applied for group discrimination and identifying sources of variation to identify the impact of PEN. We also investigated the correlation of metabolites with inflammation markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin. After 12 months, our results show substantial difference between PEN and non-PEN groups in the metabolome of CD patients in remission or with mild disease activity. Inflammatory markers were associated with individual compounds and chemical classes such as isoprenoids and phospholipids. Identified compounds comprise metabolites produced by human or bacterial metabolism, as well as xenobiotics recognized as flavoring agents and environmental contaminants and their biotransformation products. Further longitudinal studies that also include patients with higher disease activity are warranted to evaluate the suitability of these metabolic biomarkers for predicting disease activity.

Exclusive enteral nutrition remodels the intestinal flora in patients with active Crohn's disease

“…Intestinal symbiotic bacteria can inhibit the growth of pathogenic bacteria and maintain intestinal homeostasis [ 13 ]. Short-chain fatty acid (SCFA) represents metabolites produced by the intestinal flora and might occupy an important position in the occurrence and development of CD [ 14 – 16 ]. According to Ceylan Tanes et al [ 17 ], EEN or other special dietary might change the structure of specific metabolites by affecting the microbiome of healthy volunteers, thus affecting the inflammatory process.…”

The Role of Intestinal Microbial Metabolites in the Immunity of Equine Animals Infected With Horse Botflies

“…Thus, the flavonoids identified in this study should be from the food of horses. It has been reported that fatty acids and isoprenoids can be involved in many physiological and immune processes ( 53 , 54 ). Isoflavonoids possess a wide range of pharmacological properties, such as antibacterial function ( 55 ), which can alter the symbiosis relationship among microbes.…”

Transcriptomic and metabolomic analyses for providing insights into the influence of polylysine synthetase on the metabolism of Streptomyces albulus

“…Incidentally, only two of them are known metabolites: Asp Phe Ser Leu and withaperuvin E. The function of the short peptide is unknown. Withaperuvin E, a plant-derived C28 steroidal lactone [ 46 ] belonging to a family of compounds with potential anti-inflammatory activity, is mediated by the inhibition of the tumor necrosis factor alpha (TNF-α)-induced nuclear factor kappa B (NF-κB) activity [ 47 , 48 ]. Our findings suggest the existence of the synthetic gene cluster of withaperuvin E in S. albulus CICC11022, and the synthesis of this substance has a certain coupling relationship with Pls.…”