Microbiome research has been making significant strides in recent years, with a shift towards understanding the molecules produced by the microbes living in our bodies.
These molecules play a crucial role in influencing our health by interacting with our cells.
However, identifying these molecules has been a challenging task.
Traditional metabolomics studies, which focus on analyzing metabolites (small molecules) produced by microbes, can only capture about 10% of the molecular data from the human microbiome.
A breakthrough study published in Nature by microbiome experts at the University of California San Diego introduces a novel approach known as “reverse metabolomics.”
This innovative technique combines organic synthesis, data analysis, and mass spectrometry to better understand the molecules secreted by the microbiome and their impact on human health.
In their pioneering application of reverse metabolomics, the researchers uncovered hundreds of molecules that had never been observed in the human body before.
This newfound data allowed them to identify a unique metabolomic signature associated with inflammatory bowel disease (IBD).
These molecules have the potential to serve as biomarkers for diagnosing IBD or as targets for developing new therapies to treat the disease.
“We understand the importance of the microbiome, but we still lack knowledge about the specific molecules produced by these microbes and their influence on the human body,” explained senior author Pieter C. Dorrestein, Ph.D., a professor at UC San Diego.
“Reverse metabolomics enables us to identify these molecules, predict their microbial sources, and establish connections between these metabolomic signatures and health conditions.”
In a conventional metabolomics study, scientists use mass spectrometry to identify various molecules in a sample.
Each molecule has its own unique “barcode” for identification, but understanding what these barcodes represent remains a challenge.
In this groundbreaking study, researchers took a different approach. They began by synthesizing thousands of different molecules from four specific classes. Each synthetic molecule was assigned a unique barcode.
They then searched publicly available metabolomics data, including data from the Crohn’s & Colitis Foundation, for these new barcodes.
The results revealed the presence of 145 synthesized bile acids in biological samples from the public data, with 139 of them being entirely new discoveries.
These newly identified molecules are not found in biology textbooks, making them remarkable additions to our understanding of human physiology.
Further analysis demonstrated a strong association between a class of microbial molecules called bile amidates and IBD. This association was confirmed across multiple patient cohorts, suggesting that these molecules are involved in IBD’s pathology.
Digging deeper, the researchers noticed that certain bile amidates were elevated in patients with Crohn’s disease during active symptoms but not in those with ulcerative colitis. This observation could potentially aid in differentiating and diagnosing specific types of IBD.
Additional experiments indicated that several bile amidate compounds might promote gut inflammation by affecting T cell function, a crucial immune response component. Understanding these molecular mechanisms could pave the way for new therapies for IBD.
The authors believe the molecules they’ve identified could inspire the development of novel treatments for IBD.
Patients might receive pills containing live microbes that produce specific molecules or drugs that target the enzymes interacting with these disease-associated molecules.
This groundbreaking research, driven by reverse metabolomics, holds promise for both diagnosing and treating IBD, showcasing the potential of precision medicine in the field of microbiome research.
If you care about health, please read studies about how junk food harms your gut health, and how probiotics can protect gut health.
For more health information, please see recent studies about how fiber affects weight loss and your overall health, and results showing why a glass of red wine is good for your gut.
The research findings can be found in Nature.
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