Researchers from Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California (UC) San Diego have discovered thousands of previously unknown bile acids, a type of molecule used by our gut microbiome to communicate with the rest of the body. The findings can build a better understanding of our gut microbiome and may lead to the development of therapeutics for diseases that are related to the gut microbiome such as type 2 diabetes, intestinal bowel diseases, and more.

The findings are published in Cell in an article titled, “The underappreciated diversity of bile acid modifications.”

“The repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized,” the researchers wrote. “To address this knowledge gap, we created a reusable resource of tandem mass spectrometry (MS/MS) spectra by filtering 1.2 billion publicly available MS/MS spectra for bile-acid-selective ion patterns.”

“Bile acids are a key component of the language of the gut microbiome, and finding this many new types radically expands our vocabulary for understanding what our gut microbes do and how they do it,” said senior author Pieter Dorrestein, PhD, professor at Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of pharmacology and pediatrics at UC San Diego School of Medicine. “It’s like going from ‘See Spot Run’ to Shakespeare.”

Until now, the rich diversity and range of functions of secondary bile acids have been underappreciated by scientists.

This research was completed by members of the Dorrestein lab (from left to right: Helena Mannochio-Russo, Ipsita Mohanty, Lee Hagey, and Pieter Dorrestein). [UC San Diego Health Sciences]
“When I started working in the lab, there were about a few hundred known bile acids,” said study co-author Ipsita Mohanty, PhD, a postdoctoral researcher in the Dorrestein lab. “Now we’ve discovered thousands more, and we’re also working toward realizing that these bile acids do so much more than just help with digestion.”

In addition to aiding digestion, bile acids are also important signaling molecules that help regulate the immune system and serve important metabolic functions.

“Because of their interaction with our microbiome, the influence of bile acids spreads far beyond the digestive system, and so could the diseases we treat with them—the list of diseases related to bile acids is a mile long, and there are several FDA approvals for these kinds of acids as treatments,” said co-author Helena Mannochio-Russo, PhD, also a postdoctoral researcher in the Dorrestein lab.

In order to discover these molecules, the researchers leveraged the unique resources of UC San Diego. Dorrestein is director of the Collaborative Microbial Metabolite Center (CMMC), a first-of-its-kind collaboration between UC San Diego and UC Riverside that seeks to gather and centralize information about the metabolites that microbes produce to help researchers learn more about their impact on human health and the environment.

“In other areas of biology like genomics, sharing data is common, but there hasn’t been an infrastructure in place for microbial metabolomics researchers to share data until now,” said Dorrestein. “Ultimately these breakthroughs are the result of a convergence of collaboration and computing power, and we expect many more breakthroughs to come out of the CMMC.”

“We’re rewriting the textbook of human metabolism,” said Dorrestein. “If you’d have spoken to me a few years ago, I would have said we were decades away from solving this puzzle, but now, it could happen within five years. It’s really a remarkable change in our capabilities, and we believe it’s going to revolutionize the way we approach disease.”

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