Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease

Abstract

Liver disorder often occurs in patients with inflammatory bowel disease (IBD); however, the changes in IBD-induced liver disorder at the intrinsic molecular level (chiefly metabolites) and therapeutic targets are still poorly characterized. First, a refined and translationally relevant model of DSS chronic colitis in C57BL/6 mice was established, and cecropin A and antibiotics were used as interventions. We found that the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the liver tissues of mice were highly increased in the context of DSS treatment but were lowered by cecropin A and antibiotics. Subsequently, an untargeted metabolomics analysis was performed by UPLC–Orbitrap–MS/MS to reveal the metabolic profile and attempt to find the potential therapeutic targets of the liver disorders that occur in IBD. Notably, 133 metabolites were identified by an integrated database. Metabolism network and pathway analyses demonstrated that the metabolic disturbance of the liver in IBD mice was mainly enriched in bile acid metabolism, arachidonic acid metabolism, amino acid metabolism, and steroid hormone biosynthesis, while those disturbances were regulated or reversed through cecropin A and antibiotic treatment. Furthermore, the top 20 metabolites, such as glutathione, maltose, arachidonic acid, and thiamine, were screened as biomarkers via one-way analysis of variance (one-way ANOVA, p<0.05) coupled with variable importance for project values (VIP >1) of orthogonal partial least-squares discriminant analysis (OPLS-DA), which could be upregulated or downregulated with the cecropin A and antibiotics treatment. Spearman correlation analysis showed that the majority of the biomarkers have a significant correlation with cytokines (TNF-α, IL-1β, IL-6, and IL-10), indicating that those biomarkers may act as potential targets to interact directly or indirectly with cecropin A and antibiotics to affect liver inflammation. Collectively, our results extend the understanding of the molecular alteration of liver disorders occurring in IBD and offer an opportunity for discovering potential therapeutic targets in the IBD process.

Milk Fat Globule Membrane Attenuates Acute Colitis and Secondary Liver Injury by Improving the Mucus Barrier and Regulating the Gut Microbiota

“…Recently, it has been reported that many IBD patients also suffer from a secondary liver injury ( 43 ). Consistent with previous studies, the hepatic histological damage was observed in DSS-induced murine colitis model ( 43 , 44 ). AST and ALT always seemed like sensitive indicators to access the hepatic damage ( 45 , 46 ).…”

Integrated Metagenomics and Metabolomics to Reveal the Effects of Policosanol on Modulating the Gut Microbiota and Lipid Metabolism in Hyperlipidemic C57BL/6 Mice

“…To analyze the differences in gut microbiota and serum metabolites in different groups, principal component analysis (PCA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed and the over fitting of the model is verified by cross-validation (permutation test) using SIMCA-P (16.0.2, Sartorius Stedim Data Analytics AB, Umea, Sweden) ( 23 ). Then, univariate statistical analysis was used to screen metabolic markers with significant differences in accordance with our previous study ( 24 , 25 ). Briefly, based on OPLS-DA, the variable importance in the projection (VIP)>1, the relative abundance fold change of the metabolites of <0.5 or >2, and a p-value <0.05 were defined as differences.…”

Identification of trans-genus biomarkers for early diagnosis of intestinal schistosomiasis and progression of gut pathology in a mouse model using metabolomics

“…The primary bile acid biosynthesis and steroid biosynthesis were similar to the previous time-points, which might be caused by the aforementioned mechanisms. Regarding steroid hormone biosynthesis and arachidonic acid metabolism, these 2 pathways are well-known for their active roles in inflammation [ 46 – 47 ]. During this period, eggs of parasite were produced and released to intestinal lumen, leading to inflammation of the organ.…”