Last month, I visited the University of North Carolina’s Nutrition Research Institute (NRI) and learned how scientists are using cutting-edge methods to advance precision nutrition. This area of research, which falls under precision medicine, consists of shedding light on the causes of differences in metabolism and nutritional needs in individuals. The ultimate goal is to develop targeted nutritional interventions that improve health on a personalized level.
Precision nutrition research is complex because it must consider multiple factors that can affect our response to food, such as genetics, epigenetics, metabolic processes, and environmental exposures. Susan Sumner, Ph.D., professor of nutrition at the NRI, is working to untangle this complexity. She is an expert in metabolomics, ie the large-scale study of all the metabolites of a biological sample. Such analysis is an essential part of the precision nutrition toolbox.
Understanding how exposures disrupt metabolism and cause potentially harmful biological changes can provide insight into which foods can help reduce these effects. Metabolomics is an important framework for learning what an individual’s dietary needs may be in the context of multiple environmental influences ranging from lifestyle factors such as alcohol and tobacco consumption to microbiome and food pollution. the air.
Sumner arranged my visit to NRI, which is located in Kannapolis, North Carolina. I was joined by my colleague Geoffrey Ginsburg, MD, Ph.D., who is the medical and scientific director of the National Institutes of Health All of us Research program. This is a major research effort to advance precision medicine, which refers to the individualized diagnosis, prevention and treatment of disease. We learned how Sumner and his colleagues are helping realize the promise of precision medicine through their nutrition and metabolism research.
Afterwards, I caught up with Sumner to learn more about his efforts at the NRI, the importance of studying metabolism, how diet itself is a critical environmental exposure, how targeted nutritional interventions can help reduce potential damage from exhibits, and more. I also asked what inspired her to pursue a biomedical career (see box).
Rick Woychik: Can you describe the work you do at NRI?
Suzanne Sumner: NRI is located on the North Carolina Research Campus at Kannapolis, which was established about 12 years ago as a public-private partnership and includes eight North Carolina universities. Here, scientists conduct studies on many aspects of nutrition, and our institute focuses on precision nutrition.
In my lab, I study metabolites, which are small molecules in our bodies that result from normal metabolic processes or environmental exposures including dietary intake, supplements, medications, etc. These collective exposures can disrupt metabolism in unique ways in different people, what I call metabolic individuality. This can lead to major differences in how a given person may react to nutrition.
At NRI, we want to understand the optimal level of nutrients an individual needs, and this may depend on the person’s genetics, nutrient metabolism, and lifestyle factors such as tobacco, drugs, and alcohol. alcohol. Such exposures can interfere with nutrient absorption, metabolism, microbiome composition and activity, and other important biological processes. So when looking at this optimal level of nutrition, we would need to look at all of these things together, using an exposure framework, and consider other factors such as exercise and stage of life. , as optimal nutrient levels change over time.
RW: You mentioned the exposome, which refers to all of our environmental exposures throughout life. Can you elaborate on the importance of studying the diet itself as a type of exposure?
SS: Food may be the most important exposure people have in their daily lives, and it is certainly one of the most important. For example, the exposures we receive from food and drink provide nutrients to potentially protect us from environmental insults, or they could introduce compounds that disrupt normal metabolic processes. Of course, we know that genetics is an important determinant of disease risk, but we also know that there is a link between diet and the onset, progression and severity of various diseases.
Some environmental exposures cause inflammation, which can pave the way for disease. However, certain nutrients, such as omega-3 fatty acids, may fight inflammation. Additionally, essential nutrients and dietary phytochemicals can serve as antioxidants as they scavenge free radicals that can damage cell membranes. Also, I mentioned earlier the importance of genetics. It turns out that when certain vitamins are metabolized, they are involved in gene expression. So, for example, we have nutrients that play a role in DNA methylation, which is a type of epigenetic change, meaning it changes gene expression but not by changing the underlying genetic code. underlying.
I want to emphasize that essential nutrients are called essential because they cannot be synthesized by the body or synthesized in the amount needed by the body. These nutrients are necessary for normal growth, development and reproduction. They provide energy and serve as cofactors in hundreds of important biochemical reactions involved in normal metabolism. So if you don’t have essential nutrients at your optimal level at the right time and in the right place, your metabolism may not be working properly.
RW: Can you provide Environmental Factor readers with some examples of metabolic disturbances you have studied and potential nutritional interventions you have identified?
SS: In one study, we examined biological stool samples from obese individuals who had been diagnosed with osteoarthritis and from some individuals diagnosed as not having osteoarthritis. In the first group, we found significant metabolic disturbances linked to the excretion of the products of proteolysis, which refers to the breakdown of proteins. This indicated the potential for intestinal permeability, and this can be harmful because if you break the gut barrier, your nutrient absorption can be negatively affected. In addition, this intestinal breakdown promotes increased inflammation due to leakage of intestinal microbial products into the blood.
We were able to come up with a nutritional intervention that controlled the ratio of omega-3s to omega-6s, which meant we wanted to see more omega-3s to lower inflammation. We have also suggested a higher level of fiber in the diet as this is linked to the production of short chain fatty acids. We saw that these short-chain fatty acids and the microbes that produce them decreased in the osteoarthritis group. We also observed an association between environmentally relevant chemicals and disturbances in endogenous metabolism, which may play a role in disease onset or progression. I must stress that I am not the person who gives recommendations, because these really must be made in consultation with dietitians. These will be the people who can connect with a given community and truly understand what their needs are and what their food access situation looks like, which can inform recommendations and help reduce disparities.
Another study looked at the analysis of people with opium use disorders. We found disruptions in many metabolic pathways and based on this information, we came up with what I call a cocktail of nutrients. It would include certain vitamins, vitamin-like compounds, and other nutrients that can help stop addiction development, addiction progression, and relapse. Our findings are broadly applicable to other drugs and, to some extent, tobacco use, and we are excited to expand this work in the future.
Advancing Precision Nutrition
RW: I understand that you are participating in the National Institutes of Health Pooled Fund Nutrition for Precision Health [NPH] initiative, which will help expand All of us Research program. Can you describe the research you will conduct?
SS: My team will perform in-depth analyzes using metabolomics tools that we have developed with NIEHS support for our Human Health Exposure Analysis Resource hub. Participants in our NPH cohort will provide information on their usual diet, and we will also receive data on physical measurements and behavioral phenotypes.
Additionally, some people will be given special diets, which will provide insight into how individuals respond to their nutrition in combination with factors such as tobacco, drugs, medications, and other environmental exposures. We will analyze the metabolic effects of study participants’ diets and see how the effects vary with their diets and exposures.
A key aspect of NPH is that there are participating clinical sites across the country, and we plan to include a diverse population. This will allow us to dive deep into precision nutrition, and I believe it will lead to important discoveries. I am thrilled that our team at UNC Chapel Hill and the NRI are contributing to this project, and I look forward to seeing the scientific progress.
[ PubMed ]Rushing BR, McRitchie S, Arbeeva L, Nelson AE, Azcarate-Peril MA, Li YY, Qian Y, Pathmasiri W, Sumner SCJ, Loeser RF. 2022. Fecal metabolomics reveals products of dysregulated proteolysis and altered microbial metabolism in obesity-related osteoarthritis. Osteoarthritis Cartilage 30(1):81–91.
Li YY, Ghanbari R, Pathmasiri W, McRitchie S, Poustchi H, Shayanrad A, Roshandel G, Etemadi A, Pollock JD, Malekzadeh R, Sumner SCJ.. 2020. Untargeted metabolomics: biochemical disturbances in opium ssers from the Golestan cohort study inform intervention strategies. Front nut 7:584585.