Serum Bile Acid Metabolites Predict the Therapeutic Effect of Mesalazine in Patients with Ulcerative Colitis.

Ulcerative colitis (UC) is a systematic chronic disease characterized by insufficient intestinal absorption, and mesalazine is a common medical treatment. In the present study, 20 normal healthy controls (NC group), 10 unmedicated UC patients (UC group), and 20 mesalazine-responsive and 20 mesalazine-nonresponsive UC patients were recruited. A total of 42 serum BA metabolites, including 8 primary bile acids and 34 secondary bile acids (SBAs), were quantitatively measured. Compared with the NC group, serum SBAs in the UC patients were significantly lower but increased after mesalazine therapy. Differences in the serum TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S metabolites were found between the UC and NC groups, with AUC values of 0.777, 0.800, 0.815, 0.775, and 0.740, respectively. Furthermore, we identified 12-keto LCA as a specific BA marker of UC and BA biomarkers of mesalazine responsiveness. It was concluded that serum SBAs were decreased in UC patients, and TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S might aid in the diagnosis of UC. The abundance of SBAs increased after the mesalazine therapy, and serum 12-keto LCA was identified as an alternative invasive biomarker associated with UC diagnosis and therapeutic response, thereby providing a new approach for the prediction of response to mesalazine therapy in UC patients.

Metabolic analysis of early nonalcoholic fatty liver disease in humans using liquid chromatography-mass spectrometry.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disease that affects 20-30% of individuals worldwide. Liver puncture remains the gold standard for the diagnosis of liver diseases despite limitations regarding invasive nature and sample variability. It is of great clinical significance to find noninvasive biomarkers to detect and predict NAFLD. OBJECTIVE: The aims of this study were to identify potential serum markers in individuals with early-stage NAFLD and to advance the mechanistic understanding of this disease using a high-throughput mass spectrometry-based untargeted metabolomics approach. METHODS: One hundred and twelve patients with early-stage NAFLD aged 18-55 were recruited according to the guidelines. The control group included 112 healthy participants. The demographic, anthropometric, clinical and laboratory data of all participants were systematically collected. Serum samples were obtained after an overnight fast. The comprehensive serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. The resultant data was processed by Compound Discover and SIMCA-P software to validate the potential biomarkers. Significantly altered metabolites were evaluated by variable importance in projection value (VIP > 1) and ANOVA (p < 0.01). Pathway analysis was performed using MetaboAnalyst 4.0. RESULTS: The liver function test of early NAFLD patients showed no statistical differences to control group (p > 0.05). However, obvious differences in blood lipids were observed between subjects with NAFLD and controls (p < 0.001). In total, 55 metabolites showed significant changes in experimental group were identified. The area under curve (AUC) values deduced by receiver operating curve (ROC) analysis indicated that these newly identified biomarkers have high predictability and reliability. Of these, 15 metabolites with AUC greater than 0.9 were of great diagnostic value in early NAFLD patients. CONCLUSION: In this study, a total of 15 serum metabolites were found to strongly associate with early NAFLD. These biomarkers may have great clinical significance in the early diagnosis of NAFLD, as well as to follow response to therapeutic interventions.

Metabolomics window into the diagnosis and treatment of inflammatory bowel disease in recent 5 years.

Inflammatory bowel disease (IBD) is a kind of chronic inflammation that occurs in gastrointestinal tract, including Ulcerative colitis (UC) and Crohn's disease (CD). Although UC and CD are associated with intestinal inflammation and epithelial damage, they are quite different. The etiology of IBD has not been fully determined, but there is extensive evidence that its pathogenesis involves environmental, genetic, immune and microbial factors. The diagnosis and treatment of IBD is challenging due to its recurrent episodes and complex evolution. Metabolomics, as a new developing technology, can be used to qualitatively and quantitatively study small metabolic molecules in samples of patients, which include stool, urine, serum, plasma and tissues, and is increasingly valued in the diagnosis and treatment of IBD. This article sums up the recent progress of metabolomics in helping to diagnose and treat IBD diseases, hoping to provide biomarkers and new targets for the diagnosis and treatment of IBD. In addition, we present the limitations of the current study of metabolomics and highlight some solutions.

Animal models of cathartic colon.

The incidence of cathartic colon has been increasing, but satisfactory treatments are still lacking. In order to study the pathological mechanisms of the disorder and identify effective treatment methods, researchers have established different animal models of cathartic colon. This minireview briefly summarizes several common cathartic colon animal models, induced with anthraquinone laxatives such as rhubarb, total anthraquinone, rhein, and emodin, or induced with diphenylmethane laxatives such as phenolphthalein. The advantages and limitations of these models are evaluated and analyzed. We hope that this review will facilitate the selection of suitable models and improve relevant modeling methods. We anticipate the development of more convenient and stable models that can reflect the characteristics of cathartic colon in humans, and serve as useful tools for further studies.

CMTM6 significantly relates to PD-L1 and predicts the prognosis of gastric cancer patients.

BACKGROUND: The CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is a key regulator of the programed death receptor ligand-1 (PD-L1) protein. However, the usefulness of CMTM6 expression as a prognostic indicator and the relationship between CMTM6 and PD-L1 expression in gastric cancer (GC) remains unclear. OBJECTIVES: We evaluated the expression and prognostic implications of CMTM6 in GC tissue and its relationship with PD-L1 expression. PATIENTS AND METHODS: The protein expressions of CMTM6 and PD-L1 were detected in 122 cases of postoperative GC tissue using immunohistochemical (IHC) assays. Kaplan-Meier survival analysis was used to calculate the survival probability and a log-rank test was used to compare the survival curves. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the clinically-related factors associated with survival. Pearson's correlation was used to determine the correlation analysis and estimate the statistical significance. The univariate and multivariate logistic regression analyses were used to analyze the relationship between clinically-related factors and PD-L1 expression. RESULTS: Kaplan-Meier survival analysis showed that patients with high CMTM6 expression had shorter overall survival (OS) than those with low expression (P < 0.001). The expression of CMTM6 was an independent risk factor for prognosis in multivariate Cox proportional hazard regression analyses (HR:2.221, CI% [1.36-3.628], P = 0.001). The OS of patients with positively expressed PD-L1 was significantly shorter than those with negatively expressed PD-L1 (P = 0.003). The expression of CMTM6 was significantly related to the positive expression of PD-L1 in gastric cancer tissues (r = 0.186, P = 0.041). The expression of CMTM6 was the independent risk factor for PD-L1 expression in multivariate logistic regression analysis (OR:2.538, CI% [1.128-5.714], P = 0.024). CONCLUSION: CMTM6 expression is significantly related to PD-L1 and may be a useful prognostic indicator and a specific therapeutic target for cancer immunotherapy for GC patients.

Gut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment.

Mesalamine has been well used in the improvement of ulcerative colitis (UC) in clinics, however, the underlying mechanisms were not well illustrated. To explore its efficacy from the perspective of gut microbiota and related metabolites, we employed 16S rRNA sequencing and metabolomics approaches in stool samples across 14 normal healthy controls (NC group), 10 treatment-naïve UC patients (UC group) and 14 UC patients responded to mesalamine treatment (mesalamine group). We noted that the gut microbiota diversity and community composition were remarkably perturbed in UC group and partially restored by mesalamine treatment. The relative abundance of 192 taxa in genus level were significantly changed in UC group, and 168 genera were significantly altered after mesalamine intervention. Meanwhile, a total of 127 metabolites were significantly changed in UC group and 129 metabolites were significantly altered after mesalamine treatment. Importantly, we observed that many candidates including 49 genera (such as Escherichia-shigella, Enterococcus and Butyricicoccus) and 102 metatoblites (such as isoleucine, cholic acid and deoxycholic acid) were reversed by mesalamine. Spearman correlation analysis revealed that most of the candidates were significantly correlated with Mayo score of UC, and the relative abundance of specific genera were significant correlated with the perturbation of metabolites. Pathway analysis demonstrated that genera and metabolites candidates were enriched in many similar molecular pathways such as amino acid metabolism and secondary metabolites biosynthesis. Importantly, ROC curve analysis identified a gut microbiota signature composed of five genera including Escherichia-Shigella, Streptococcus, Megamonas, Prevotella_9 and [Eubacterium] _coprostanoligenes _group which might be used to distinguish UC group from both NC and mesalamine group. In all, our results suggested that mesalamine might exert a beneficial role in UC by modulating gut microbiota signature with correlated metabolites in different pathways, which may provide a basis for developing novel candidate biomarkers and therapeutic targets of UC.