A Q&A with Giulia Menichetti, PhD
Giulia Menichetti, PhD, of the Channing Division of Network Medicine at Brigham and Women’s Hospital, is a statistical and computational physicist.
Her research examines the chemical complexity of food and aims understand its impact on health.
She recently published a study in the New England Journal of Medicine, Chemical Complexity of Food and Implications for Therapeutics, that discusses how a systematic analysis of food–chemical interactions could potentially advance nutrition science and drug discovery.
We asked her a few questions about the work.
Q: Why is it important to understand the chemical makeup of food?
Diet plays a central role in shaping health, yet most research focuses on a key but narrow subset of nutrients—those that serve as energy sources, supply essential amino acids for growth and repair, or regulate enzyme activity.
These components are undoubtedly important, but they represent only a fraction of what food actually contains.
Our work has shown that food we eat harbors over 139,000 distinct molecules, the vast majority of which are not tracked in standard nutritional databases.
These compounds do not just fuel the body—they modulate the gut microbiome, interact with human proteins, and regulate a vast array of subcellular processes.
In terms of mechanisms of action, many of these molecules behave less like standard nutrients and more like drugs.
Although the Human Genome Project revolutionized our understanding of genetic risk, it turns out that genes only explain about 10% of overall disease risk. The other 90% is largely shaped by environmental exposures, with diet being a significant contributor.
If we want to build on the success of genomic science, we need to look at food differently.
It is not just a source of calories or vitamins, but a chemically rich system, full of compounds that can influence health in ways we are only beginning to understand.
Uncovering and mapping these molecules is key to unlocking the next generation of discoveries in nutrition and medicine.
Q: What Is Nutrition Dark Matter (NDM) and how does it relate to food science?
Nutrition Dark Matter, or NDM, refers to the vast number of chemical compounds in food that are largely untracked by epidemiological studies and traditional food composition databases.
Most food composition databases focus on around 150-180 well-known components, such as calories, fats, proteins, vitamins and minerals.
In 2019, we coined the term nutritional dark matter to draw attention to the much broader chemical diversity in food that remains unexplored.
Despite increased efforts since 2003 to map the small-molecule content of food, such as polyphenols, the full range of compounds we consume is still mostly unknown.
To begin addressing this gap, we built the NDM library, a resource of more 139,000 unique chemicals, each with a valid international chemical identifier, spanning over 3,000 common foods and 17,000 taxonomic species.
This chemical layer extends far beyond what is listed on nutritional labels, containing compounds that have clear pharmacological activity.
For example, among the adrenergic agents—drugs that activate the sympathetic nervous system—we find tyramine, an organic compound that functions as a neurotransmitter and is common in foods that are fermented, cured, pickled, or aged, and synephrine, which is found in oranges and other members of the citrus family.
NDM changes food science by viewing food as a complex biochemical system rather than just fuel or isolated nutrients.
It considers nutrition as part of human-environment co-evolution, where food molecules serve as signals that our bodies interpret and adapt to.
Q: How do ultra-processed foods affect our health (and why are they so tempting to eat)?
One theory on the hyper-palatability of ultraprocessed foods or UPFS, is that high energy density and rich salt, sugar and fat content overrides satiety signals—our natural feelings of fullness—leading to overeating.
Hyper-palatability also involves physical changes to food that alter the natural food matrix, affecting digestion, absorption, and satiety.
UPFs often have textures that encourage fast eating and may include additives such as sweeteners and emulsifiers that disrupt gut health and metabolic function.
Understanding these impacts requires comprehensive data on food composition and production.
Q: What are the fundamental differences in the roles of drugs and food molecules?
Drugs are typically engineered or selected for high specificity--to bind to a small number of protein targets associated with disease. This approach aims to reduce off-target effects and side effects.
A common approach in pharmaceutical development, known as “me-too chemistry,” involves making incremental modifications to existing drug structures to refine their activity.
While this is effective for precision targeting, the strategy inherently limits the structural diversity of drug compounds.
Food molecules have evolved over millions of years, leading to greater chemical diversity that still supports optimal protein binding.
Unlike drugs, food molecules possess diverse structures and interact with numerous targets, entering the body as complex mixtures rather than highly specific compounds.
Q: What key questions remain?
One of the most urgent questions is: What do all these untracked food compounds actually do in the body?
We know that many have drug-like properties, with their biological effects shaped by their structure and transformation through human and microbial metabolism.
The metabolites and byproducts that emerge during the digestive process—often entirely different from the original compounds—may be the true drivers of physiological effects, yet remain almost entirely uncharted.
This points to a larger unknown: How does metabolism—both human and microbial—modify, amplify or suppress the activity of food compounds? Understanding these transformations is crucial.
Two people consuming the same food can experience different molecular exposures depending on their microbiome, enzyme expression or even what else they eat at the same meal.
To learn more, we must confront a fundamental data gap—one that spans the entire food-biology interface. Most food molecules are still not systematically tracked across different foods and processing states.
For the few that are, we have limited knowledge of their human and microbial protein targets.
Even when targets are known, we lack a comprehensive map of the metabolic pathways, both human and microbial, that transform these compounds into potentially active or inactive metabolites.
Filling this knowledge gap is our research mission for the years to come.
Additional resources:
Research at Mass General Brigham
At Mass General Brigham, research isn’t just about discovery—it’s about transforming patient care worldwide.
With a community of more than 3,700 Principal Investigators and 16,000 scientists, we are pioneering discoveries in fields ranging from AI and gene therapy to cancer, neuroscience, and global health.
Through collaboration, innovation, and a relentless pursuit of knowledge, we turn groundbreaking ideas into real-world impact. Follow us for the latest research insights, clinical advancements, and stories of discovery from across Mass General Brigham.
Leave a Comment