Alterations of metabolites related to microbiota–gut–brain axis in plasma of colon cancer, esophageal cancer, stomach cancer, and lung cancer patients

Co-occurring symptoms such as depression, anxiety, fatigue, and sleep disorders are frequently comorbid with cancer. The causes of these cancer-related symptom clusters are hypothesized sharing a common biological mechanism. This study explored pattern differences of some gut metabolites (glucocorticoids, short-chain fatty acids, gut microbial metabolites from tryptophan) in plasma samples from patients with four types of cancer. Metabolomics analysis was performed to indicate the differences of metabolites. Discrimination model and diagnostic model were constructed using orthogonal partial least squares discriminant analysis, and differential metabolites were screened, then receiver-operating characteristic curve analysis was performed to evaluate the performance of these models. Melatonin (MLT), indole propionic, and skatole were screened as the common differential metabolites shared by four types of cancer, indicating that the intestinal microbial metabolic pathway of tryptophan plays a key role in the occurrence and development of malignant tumors. The area under the curve values for the potential candidate biomarker predictors in univariate analysis ranged from 0.771 to 0.989, and in multivariate analysis ranged from 0.985 to 1.00. The sensitivity and specificity of the multivariable model were 94.7-100 and 96.4-100%, respectively. These biomarkers also had good performance in discriminating different pairs of cancer. The analysis of gut microbiota metabolites allows us to characterize the common metabolic characteristics of patients with various cancers. The intestinal microbial metabolic pathway of tryptophan plays a key role in the occurrence and development of malignant tumors.