(492f) Using Metabolomics and 16S rRNA Sequencing to Investigate the Impact of Environmental Chemical Perturbations on Gut Microbiota Community Composition and Function

Recent findings suggest that a significant alteration of the gut microbiota, or dysbiosis, contributes to various diseases and disorders, including developmental disorders of the brain. Dysbiosis may result from infection, diet, or other environmental perturbations. One example of an environmental perturbation is exposure to biologically active synthetic chemicals present in household and commercial products. In recent years, exposure to these chemicals, labeled as endocrine disrupting compounds, have emerged as a significant public health concern. Interestingly, several of these chemicals, e.g. bisphenol A and phthalate esters, have been linked to neurodevelopmental disorders, including autism spectrum disorder (ASD).

This presentation describes a study on the effects of di-ethylhexyl phthalate (DEHP), a ubiquitous plasticizer. The effects of this chemical were studied in an in vitro culture model of the gut microbiota. Using 16S rRNA sequencing and untargeted LC-MS based metabolomics, we found that DEHP significantly modifies both the microbiota community structure as well as metabolic profile. Applying a novel metabolomics data annotation tool developed in our laboratory, we confidently identified more than 100 products of microbiota metabolism. Co-analyzing the 16S and metabolomics data using a metabolic model of the microbiota revealed that the chemically induced increases and decreases in specific metabolites can be attributed to the depletion or enrichment of particular groups of bacteria. Notably, DEHP exposure significantly increased the level of p-cresol, while expanding the abundance of Clostridium bolteae, both of which have been identified recently as potential biomarkers of ASD. Our results suggest that environmental chemicals could cause significant dysbiosis of the gut microbiota leading to an altered milieu of bioactive metabolites in the intestine, consistent with other studies linking environmental chemical exposure to developmental disorders involving gastrointestinal conditions.