Miguel G. Rodriguez Reyes

Miguel G. Rodriguez Reyes, a junior industrial biotechnology major at University of Puerto Rico at Mayaguez, set out to explore the connection between the gut commensal Ruminococcus gnavus and inflammatory bowel disease.

The cause of inflammatory bowel disease (IBD) is unclear; however, environmental, genetic and microbiome factors have been linked to the disease. Working at the Broad meant working at the cutting edge of science. Using advanced techniques and asking ambitious questions, scientists in every discipline here make a real impact in the world of human disease. The collaborative and diverse community here create an environment where the possibilities of what we can achieve become unimaginable. The Broad taught me how to be a better scientist: Always look at the big picture and ask challenging questions.To explore the combination of these factors, the IBD Human Microbiome Project characterized IBD and non-IBD patients using omics approaches. Applying the metabolomics platform to these samples revealed hundreds of unknown metabolites associated with IBD, resulting in a need of means to identify them. In this project, we assessed the contribution of the commensal gut bacteria Ruminococcus gnavus to the stool metabolome of IBD patients. We applied a platform comprised of four complementary non-targeted high-resolution mass spectrometry liquid chromatography methods to Ruminococcus gnavus and IBD stool samples. This approach produced measurements of hundreds of small molecules and thousands of yet-to-be identified features. All features present in bacteria were aligned in silico with the ones in stool, and confirmed experimentally by matching their fragmentation pattern in tandem MS experiments and elution profile. Finally, fragmentation libraries of all matching metabolites were produced in order to create an annotation resource for further compound characterization. This approach allowed us to align hundreds of metabolic features present in both Ruminococcus gnavus and IBD stool, suggesting that they are produced by the bacteria. These results provide means for annotating unknown stool molecules strongly associated with IBD and provide a mechanistic connection between Ruminococcus gnavus metabolism and IBD. This method can be used with other gut bacteria to identify the source of unknown IBD associated metabolites with the hope of elucidating the pathogenesis of the disease.

Project: Identification of metabolites associated with inflammatory bowel disease Produced by the gut commensal Ruminococcus gnavus

Mentors: Julian Avila-Pacheco and Clary Clish, Metabolomics Platform