Unlocking the small molecules: Metabolomics for precision health

Last week, Dr. David Wishart, a leading metabolomics expert, shared insights into his lab's work at the University of Alberta during a talk hosted by the National Institutes of Health Office of Dietary Supplements​. The focus was on how metabolomics, dietary supplements and online databases are advancing precision nutrition.

“Targeted metabolomics offers a powerful, inexpensive route to understand the composition of food, drugs and supplements to measure how much has been consumed and assess its impact on human physiology or metabolism,” he explained, emphasizing the considerable evolution from conventional methods like questionnaires and recalls.

Instead of DNA or RNA sequencing, this quantitative approach uses high throughput technologies such as mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography or gas chromatography to identify much smaller molecules in fluids, cells, tissues or entire organisms.

‘Canaries of the genome’​

Within the study of genomics, proteomics and other disciplines in the field of biological sciences, Dr. Wishart places metabolomics at the top of the “omics pyramid”, or as he calls it “the pyramid of life”.  

Whereas the genome (the genetic information of an organism) is barely influenced by external factors, he said, there is progressively greater influence of diet, environment, microbiome and physiology as you climb the pyramid. Within this hierarchy, he described metabolites as the “canaries of the genome” owing to their role as early indicators of physiological and metabolic changes in the body. 

"The 'canary of the genome' concept is that metabolites are greatly amplified, so a single mutation at the DNA level can lead to about a 10,000-fold change in certain metabolites," he explained, highlighting the potential of metabolomics in monitoring genetic and environmental influences. 

The Wishart lab’s work to identify 250,000 small molecules (endogenous, microbial and dietary) in the human body began nearly 20 years ago and is now archived in the open access online Human Metabolome Database (HMDB). The project has since expanded into creating other publicly available databases that characterize hundreds of thousands of metabolites associated with food, drugs, cannabis and supplements.

Supplement specific​

One of these databases is the Natural Products Magnetic Resonance Database (NP-MRD)​. Launched in 2020, it includes over 281,000 compounds to date, complete with descriptions and potential applications for health. 

Dr. Wishart referenced popular supplements like multivitamins, beet extracts, creatine, probiotics, fish oil, turmeric, melatonin and polyphenols, illustrating that each has its own set of intake biomarkers—whether fecal SCFAs, lactate or indole and cresol derivatives for probiotics or betaine, dimethylglycine, sarcosine and homocysteine for beet extracts.

The impact of a supplement like beet extract known for reducing harmful homocysteine, for example, is then measured with the lab’s GigaAssay, which examines 1,400 metabolites tied to various pathways and health effects. 

“We can track whether someone is taking supplements or whether the supplements are being processed by their body properly, or whether they’re taking too much or too little,” Dr. Wishart said. 

Using novel machine learning for data extraction, the lab’s goal is to enrich this information to evolve the NP-MRD into a database as fully annotated as its Drugbank pharmaceutical knowledge database​—with mechanisms of action, absorption, distribution, metabolism and pharmacokinetic data—to connect compounds to diet and health.

Towards precision nutrition ​

Dr. Wishart said that while precision nutrition is often regarded as “more aspirational than actual deliverable”, the number of companies leveraging targeted metabolomics and the freely available databases continues to grow, and “a nascent precision nutrition industry is really starting to emerge”.

Within these models, many use longitudinal profiling (usually a combination of genome, metabolome, proteome or microbiome analysis) to optimize informed nutrition, supplement, exercise or medication suggestions tailored to the intra-individual variability of nutritional status in a population.

“The results that I’m seeing, and some of [the companies] are starting to publish, are actually quite encouraging, and it’s clear that measurable improvements in human health are possible through this guided, customized, individualized diet approach,” he said.

Upcoming ODS Seminar Series​ topics include “Immune System-Microbiome Interactions and Health” (Feb. 28), “Dietary Supplements: Interactions with Taste and Smell” (March 13), “Vitamin D, the Microbiota and Immune Regulation” (April 17), “Effects of Soluble Corn Fiber on Bone Metabolism in Children” (May 22) and “Botanical Dietary Supplement Safety” (June 12).