The human microbial exposome: expanding the Exposome-Explorer database with gut microbial metabolites

Abstract Background. Metabolites produced by the gut microbiota play an important role in the cross-talk with the human host. Many microbial metabolites are biologically active and can pass the gut barrier and make it into the systemic circulation, where they form the gut microbial exposome, i.e. the totality of gut microbial metabolites in body fluids or tissues of the host. A major difficulty faced when studying the microbial exposome and its role in health and diseases is to differentiate metabolites solely or partially derived from microbial metabolism from those produced by the host or coming from the diet. Objective. To collect data from the scientific literature and build a database on gut microbial metabolites and on evidence of their microbial origin. Methods : Three types of evidence on the microbial origin of the gut microbial exposome were defined: 1/ metabolites are produced in vitro by human faecal bacteria; 2/ metabolites show reduced concentrations in humans or experimental animals upon treatment with antibiotics; 3/ metabolites show reduced concentrations in germ-free animals when compared with conventional animals. Data was manually collected from peer-reviewed publications and inserted in the Exposome-Explorer database. Furthermore, to explore the chemical space of the microbial exposome and predict metabolites uniquely formed by the microbiota, genome-scale metabolic models (GSMMs) of gut bacterial strains and humans were compared. Results : A total of 1854 records on one or more types of evidence on the gut microbial origin of 462 metabolites was collected in Exposome-Explorer. Data on their known precursors and concentrations in human blood, urine and faeces was also collected. About 66% of the predicted gut microbial metabolites (n = 1543) were found to be unique microbial metabolites not found in the human GSMM, neither in the list of 462 metabolites curated in Exposome-Explorer, and can be targets for new experimental studies. Conclusion: This new data on the gut microbial exposome, freely available in Exposome-Explorer (http://exposome-explorer.iarc.fr/), will help researchers to identify poorly studied microbial metabolites to be considered in future studies on the gut microbiota, and study their functionalities and role in health and diseases.