Key Stratification of Microbiota Taxa and Metabolites in the Host Metabolic Health-Disease Balance.

Human gut microbiota seems to drive the interaction with host metabolism through microbial metabolites, enzymes, and bioactive compounds. These components determine the host health-disease balance. Recent metabolomics and combined metabolome-microbiome studies have helped to elucidate how these substances could differentially affect the individual host pathophysiology according to several factors and cumulative exposures, such as obesogenic xenobiotics. The present work aims to investigate and interpret newly compiled data from metabolomics and microbiota composition studies, comparing controls with patients suffering from metabolic-related diseases (diabetes, obesity, metabolic syndrome, liver and cardiovascular diseases, etc.). The results showed, first, a differential composition of the most represented genera in healthy individuals compared to patients with metabolic diseases. Second, the analysis of the metabolite counts exhibited a differential composition of bacterial genera in disease compared to health status. Third, qualitative metabolite analysis revealed relevant information about the chemical nature of metabolites related to disease and/or health status. Key microbial genera were commonly considered overrepresented in healthy individuals together with specific metabolites, e.g., and phosphatidylethanolamine; and the opposite, and Phosphatidic Acid, which is converted into the intermediate Cytidine Diphosphate Diacylglycerol-diacylglycerol (CDP-DAG), were overrepresented in metabolic-related disease patients. However, it was not possible to associate most specific microbiota taxa and metabolites according to their increased and decreased profiles analyzed with health or disease. Interestingly, positive association of essential amino acids with the genera were observed in a cluster related to health, and conversely, benzene derivatives and lipidic metabolites were related to the genera , , , and in a disease cluster. More studies are needed to elucidate the microbiota species and their corresponding metabolites that are key in promoting health or disease status. Moreover, we propose that greater attention should be paid to biliary acids and to microbiota-liver cometabolites and its detoxification enzymes and pathways.