San Diego Scientists' "Reverse Metabolomics" Revolution, New Hope for IBD Diagnosis and Treatment

San Diego Scientists' "Reverse Metabolomics" Revolution, New Hope for IBD Diagnosis and TreatmentSource: Znode at the English-language Wikipedia, CC BY-SA 3.0, via Wikimedia Commons
Ben J. Costas
Published on December 06, 2023

Scientists at the University of California, San Diego, are turning the tide in the battle against inflammatory bowel disease (IBD) with their innovative "reverse metabolomics" approach, as reported yesterday. This new technique is not just a shot in the arm for microbiome research but could pave the way for a more precise diagnosis and treatment of IBD—a condition that affects millions worldwide.

In a study featured in Nature via UC San Diego Today, the team showcased how they can predict and identify previously unknown molecules that are key players in human health and illness. According to senior author Pieter C. Dorrestein, Ph.D., professor at Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego, "We know the microbiome is important, but we don’t know what kinds of molecules the microbes produce or how influential they are in the human body." Reverse metabolomics aims to bridge this gap. However, typical metabolomics studies grapple with deciphering just 10% of a human microbiome sample's molecular data.

Undeterred by the complexity, the researchers synthesized thousands of molecules to define their molecular "barcodes" via mass spectrometry. They then matched these barcodes with publicly available metabolomics data. In the statement obtained by UC San Diego, Emily C. Gentry, Ph.D., now an assistant professor at Virginia Tech and first author of the study, said, "We're using organic synthesis and data science to better understand how our bodies work on a molecular level." The result was identifying a new metabolomic signature for IBD, which includes 139 never-before-seen bile acids.

Dorrestein's team discovered that certain molecules, specifically bile amidates, aren't just bystanders but could actively contribute to the development of IBD. The relationship between these molecules and the disease was validated across multiple patient cohorts. Astonishingly, these compounds were elevated in those with Crohn's disease during active symptoms, offering a potential diagnostic marker to distinguish types of IBD. Notably, one microbial compound showed a dramatic six-fold increase in a cytokine implicated in Crohn's disease, hinting at its role in gut inflammation.

As the researchers continue to unravel the mysteries of the microbiome, hope for new treatments emerges. The Crohn's & Colitis Foundation, which helped fund the study, regards the findings as a significant step forward. Andrés Hurtado-Lorenzo, Ph.D., at the Foundation, highlighted the study's potential to inspire new therapeutics. He said, "This is a remarkable achievement derived from our precision nutrition initiative, in which Dr. Dorrestein previously demonstrated that reverse metabolomics could identify food metabolites associated with disease severity in patients with IBD."