Biomarkers of Metabolomics in Inflammatory Bowel Disease and Damp-Heat Syndrome: A Preliminary Study

Abstract

Aims. This study aims to investigate the potential biomarkers of inflammatory bowel disease (IBD) and IBD with damp-heat syndrome (IBD-DH) by metabolomics. Methods. Plasma and urine samples were collected from 15 healthy controls and 30 IBD patients, including 15 IBD-DH and 15 IBD with spleen deficiency syndrome (IBD-SD), which was coded as SF8G and SF70 according to the International Classification of Diseases Eleventh Revision (ICD-11) issued by World Health Organization. Pseudotargeted metabolomics method was used based on ultra-high-performance liquid chromatography-high-resolution mass spectrometry and triple-quadrupole mass spectrometry. Results. Under the condition of false discovery rate (FDR) < 0.05, variable importance projection (VIP) > 1.0, and fold change (FC) > 1.5 or < 2/3, we found 57 plasma differential metabolites and 20 urinary differential metabolites in IBD. Then, with area under the curve (AUC) ≥ 0.85 and FC ≥ 2 or ≤ 0.3, 11 potential biomarkers were identified, such as acylcarnitine (ACar 20:4, ACar 18:1, and ACar 20:3), 3-indoleacetic acid, hippuric acid, and dehydroepiandrosterone sulfate, which is related to intestinal microbiota and immune response. However, less obvious differences were observed in IBD-DH when compared with IBD-SD. Under the condition of FDR < 0.2, VIP >1.0, and FC > 1.5 or < 2/3, we identified 16 plasma differential metabolites. In urine samples, IBD-DH and IBD-SD had the same metabolite pattern. With AUC ≥ 0.80, 7 differential plasma metabolites, mainly glycerophospholipids, were identified in IBD-DH. Kyoto Encyclopedia of Genes and Genomes analysis indicated that metabolic pathways, such as citrate cycle and amino acids metabolism, were mainly responsible for the distinction between IBD and healthy controls, whereas glycerophospholipid metabolism perturbation was not only a manifestation of IBD but also an important pathway to distinguish two subtypes defined by traditional medicine, IBD-DH and IBD-SD. Conclusion. In this study, we found that several metabolites of aromatic acids and lipid derivatives could act as potential biomarkers to discriminate IBD from healthy controls. Glycerophospholipids metabolites might be used to differentiate IBD-DH from IBD-SD.

Mapping the gut microecological multi-omics signatures to serum metabolome and their impact on cardiometabolic health in elderly adults

“… 31 Indolepropionic acid can catalyze the synthesis of indoleacetic acid. 32 Dietary indolepropionic acid supplementation attenuates atherosclerotic plaques. 33 These collectively highlight the potential of GMM-explained SMs (e.g., sebacic acid, EPA, and indoleacetic acid) in modulating cardiometabolic disease risk.…”

Metabolite Alterations in Autoimmune Diseases: A Systematic Review of Metabolomics Studies

“…However, there were instances of variation between individual cases. For instance, one of the studies reported an increase in the level of phosphatidylcholine in CSF specimens [ 35 ], while some studies observed a decrease in the level of phosphatidylcholine in tears and plasma [ 37 , 90 ]. We observed similar findings for other metabolites.…”

Inflammation and Organic Cation Transporters Novel (OCTNs)

“…Interestingly, the abundance of certain types of acylcarnitines can help to classify IBD, IBD with damp-heat syndrome (IBD-DH), and IBD with spleen deficiency syndrome (IBD-SD). Indeed, Wu et al demonstrated that three specific acylcarnitines (ACar 20:4, ACar 18:1, and ACar 20:3) were significantly increased in IBD plasma samples and that the ACar 8:1 was significantly increased in IBD with damp-heat syndrome when compared with IBD with spleen deficiency syndrome [141]. Another study found that the fecal acylcarnitine content in patients with IBD and mice with experimental colitis tended to increase compared to the control group, and the reason may be related to intestinal inflammation that led to mitochondrial dysfunction in the apical domain of the surface epithelium that may reduce the consumption of fatty acids [86].…”