Human metabolism is a complex web of chemical processes and interactions between our cells and the microbes living within us. The more scientists can identify and classify the molecules involved in our metabolism, called metabolites, the more we can learn about human health and disease. Now, researchers at University of California San Diego have made a major advance in our understanding of human metabolism by describing hundreds of new N-acyl lipids, a type of molecule involved in immune and stress responses.
The main findings of the study, published in Cell, were:
- The researchers identified 851 distinct N-acyl lipids across various tissues and biofluids, 777 of which had never been documented before.
- Many of these new metabolites may originate from human gut microbes.
- The distribution pattern of these molecules varies based on diet, microbial colonization, and in people with diseases that impact the microbiome, such as diabetes.
“Metabolites are the language that the body uses to communicate with itself and with our microbiome, and studying them can offer significant insight into the role of microbial metabolism in health and disease,” said senior author Pieter Dorrestein, Ph.D., professor at UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences and Departments of Pharmacology and Pediatrics at UC San Diego School of Medicine. “It’s like we’ve added hundreds of new words to the metabolic dictionary.”
Human metabolism is a delicate system, and imbalances in metabolism have been linked to a wide range of diseases, including diabetes, cancer and neurological disorders. For decades, much of the underlying biochemistry of human metabolism, including the role of the human microbiome, has gone unknown, making it harder to understand and treat diseases related to metabolism.
The hundreds of new compounds help fill this knowledge gap.
“The big surprise here was how diverse this group of compounds actually is,” said first author Helena Mannochio Russo, Ph.D., a postdoctoral researcher in Dorrestein’s lab.
Read the full study.
Additional co-authors of the study include Vincent Charron-Lamoureux, Martijn van Faassen, Santosh Lamichhane, Wilhan D. Gonçalves Nunes, Victoria Deleray, Adriana V. Ayala, Yuichiro Tanaka, Abubaker Patan, Kyle Vittali, Prajit Rajkumar, Yasin El Abiead, Haoqi Nina Zhao, Paulo Wender Portal Gomes, Ipsita Mohanty, Carlynda Lee, Aidan Sund, Meera Sharma, Yuanhao Liu, David Pattynama, Gregory T. Walker, Grant J. Norton, Lora Khatib, Mohammadsobhan S. Andalibi, Crystal X. Wang, Ronald J. Ellis, David J. Moore, Jennifer E. Iudicello, Donald Franklin, Jr., Scott Letendre, Loryn Chin, Corinn Walker, Simone Renwick, Jasmine Zemlin, Michael J. Meehan, Jane J. Kim, Manuela Raffatellu, Lars Bode, Hiutung Chu, Karsten Zengler, Dionicio Siegel and Rob Knight at UC San Diego, Xinyang Song and Dennis Kasper at Harvard Medical School, Zachary Burcham at University of Tennessee Knoxville, Sejal Kadakia at Children’s Hospital of Orange County and Mingxun Wang at UC Riverside.
