Posters
« Back
Gut Microbial Metabolites and Hepatic Xenobiotic Metabolism: A High Throughput Screening Approach
EP22257
Poster Title: Gut Microbial Metabolites and Hepatic Xenobiotic Metabolism: A High Throughput Screening Approach
Submitted on 19 Sep 2014
Author(s): Glynn Martin, James Sidaway, Jonathan Swann
Affiliations: University of Reading, AstraZeneca
This poster was presented at Metabomeeting 2014
Poster Views: 2,020
View poster »


Poster Information
Abstract: Idiosyncratic drug responses leading to drug induced liver injury (DILI) occur in 15% of patients receiving drug treatments. These idiosyncratic drug reactions cannot be explained or predicted. The gut microbiome is highly host specific and is known to influence the host metabolic system including xenobiotic metabolism. Here, the potential for gut microbial-associated metabolites to impact on host drug metabolism and toxicity was explored using a novel exploratory pipeline. Candidate microbial metabolites were identified using two antibiotic-treated rodent models and a 1H NMR spectroscopy-based metabonomic approach. The modulatory potential of each metabolite was then evaluated using a high throughput in vitro screening approach following co-administration with paracetamol. Hepatic SV40 large T-antigen immortalized human liver epithelial (THLE) cell lines were used including a subline transfected with CYP2E1, a major drug metabolising enzyme. Twelve microbial metabolites were screened and one microbial metabolite, 4-cresyl, was found to increase toxicity when dosed to THLE-CYP2E1 cells. Co-administration of paracetamol with 4-cresyl resulted in a greater toxic effect compared to an equivalent dose of paracetamol or 4-cresyl alone. Through this novel screening approach microbial-associated metabolites have been identified and their potential to modulate host xenobiotic metabolism, and therefore contribute to idiosyncratic drug responses, has been evaluated.Summary: This poster highlights the combination of metabonomics and high throughput screening by the identification of gut microbial metabolites and a screening assay designed to determine their cytotoxicity to liver-like cell cultures.References: Report abuse »
Questions
Ask the author a question about this poster.
Ask a Question »

Creative Commons

Related Posters


Cytotoxicity of Environmental Toxins PFOA and Gen X
Lauren Zane, Thomas Schultz

Evaluation of Laser Cleaning of Parchment, Wool and Featherwith High Performance Liquid Chromatography and AttenuatedTotal Reflection -Fourier Transform Infrared Spectroscopy
Stamatis C. Boyatzis, Eleni Ioakimoglou, Eleni Tziamourani, Efrosini Karantoni Ekaterini Malea, Stavroula Rapti, Paraskevi Pouli, Athanassia Papanikolaou, Kristalia Melessanaki, Georgios Panagiaris

Fiber identification methodology applied on reference paper samples and works of art on paper substrate
Eleni Tziamourani, Agni Terlixi, Michalis Doulgeridis, Athina Alexopoulou

low-volume workflows improve the quality of drug discovery: two case studies
Margaret Kenney#, Archi Joardar#, Vasudeo Badarinarayana#, Joby Jenkins*

ExpiSf™ Expression system: A Chemically Defined Baculovirus-Based System for Enhanced Protein and Virus Production in Sf9 Cells
Kenneth Thompson, Maya Yovcheva, Sara Barnes, Melissa Cross, Katy Irvin, Natasha Lucki, Henry Chiou, and Jonathan Zmuda