Research Spotlight

Congratulations to Drs. Allen and Miller for receiving a 3-year federal grant from the USDA NIFA titled “Optimizing Bioactive Metabolites In Fermented Foods to Improve Human Immune Function”. The generation of preliminary data was accelerated by the Personalized Nutrition Initiative seed grant they received last year.

The primary goal of this research project is to determine if specific microbial-derived metabolites derived from aromatic amino acids (ArAA) found in fermented foods can be optimized in a whole food matrix to promote anti-inflammatory activity in humans.

Fermented food intake is associated with improvements in human immune function. These benefits may lie in bioactivity of microbe-derived metabolites (i.e., postbiotics) found in the food matrix. Their aim is 1) identify beneficial postbiotics and then 2) adapt strategies to optimize their production in a food matrix that will have a significant impact on immune health and disease prevention. Their preliminary data indicates that select fermented foods contain high concentrations of biochemically related metabolites downstream of microbial metabolism of ArAAs that they have identified as mediators of innate immune cell (monocyte) inflammatory activity. These data led them to hypothesize that there is a unique class of microbial products within fermented food that confers anti-inflammatory activity. However, how fermented food postbiotic properties can be optimized to improve immune health of humans has never been tested.

They aim to fill this knowledge gap by: 1) Further investigating the immune and metabolic tuning properties of microbial-ArAA metabolites; 2) Identifying food matrix conditions that optimize microbial ArAA metabolism, and; 3) Determining if whole fermented food diets optimized for high microbial-derived ArAA metabolites promote anti-inflammatory activity in humans.

Jacob M Allen, PhD, is an Assistant Professor in the Department of Kinesiology and Community Health. He also has affiliate appointments with the Personalized Nutrition Initiative, the Division of Nutritional Sciences, the Microbiome and Metabolic Engineering (MME) theme at the Institute of Genomic Biology (IGB), and the Microbial Systems Initiative. Dr. Allen received his bachelor’s and master’s degrees in Exercise Physiology from the University of North Carolina at Chapel Hill and his PhD in Kinesiology from the University of Illinois Urbana-Champaign. Dr. Allen completing a 3-year postdoctoral program in microbiology at Nationwide Children’s Hospital in Columbus, OH. In 2022, he received the Peter Reeds J. Young Investigator Award from the American Society for Nutrition.

Dr. Allen’s research program concentrates on specific environmental interventions and conditions: 1. Exercise, 2. Psychological Stress, and 3. Diet, that influence gut microbial communities during both homeostatic and pathological disease states. Dr. Allen’s lab is aiming to provide a new perspective into how environmental conditions interact to modify the gut microbiota, with the ultimate goal of leveraging this knowledge to improve human health.

Michael Miller, PhD, is a Professor of Food Microbiology and Associate Head for Graduate Programs in the Department of Food Science and Human Nutrition. He also has affiliate appointments with the Personalized Nutrition Initiative, the Division of Nutritional Sciences, and the Institute of Genomic Biology (IGB). Dr. Miller received a BS in Environmental Toxicology at the University of California at Davis. From there, he attended Michigan State University, where he received his PhD in Food Science and Environmental Toxicology. Dr. Miller continued his education as a post-doctoral scientist at North Carolina State University. In 2006, Dr. Miller joined the University of Illinois. He and his wife Katherine have two children, Robert and Christopher. Dr. Miller’s research involves solving problems related to various aspects of fermentation. He develops strategies to improve the safety of fermented dairy products, especially Hispanic-style cheeses. He evaluates the microbial metabolism of dietary components in the gut to maximize health benefits for humans. He develops contamination solutions for industrial fermentations.

[published in the May 2023 Newsletter]

Hannah Holscher, PhD, RD, is an Associate Professor of Nutrition in the Department of Food Science and Human Nutrition and the Division of Nutritional Sciences. She also has affiliate appointments with the Institute of Genomic Biology (IGB), the National Center for Supercomputing Application (NCSA), and the Family Resiliency Center.Research in Dr. Holscher’s laboratory, the Nutrition and Human Microbiome Laboratory, uses clinical interventions and computational approaches to study the interactions of nutrition, the gastrointestinal microbiome, and health. Her creative use of machine learning approaches to determine microbial biomarkers of food intake and human health status resulted in her recognition as a 2017 New Innovator in Food and Agricultural Research and a 2020 National Academy of Medicine Emerging Leader. Recently she received the 2021 American Society for Nutrition’s Mead Johnson Young Investigator Award for her series of work on nutrition and the human microbiome.

Ruoqing Zhu, PhD, is an Assistant Professor in the Department of Statistics, IGB, NCSA, and the Carle Illinois College of Medicine. Research in Dr. Zhu’s group focuses on statistical learning, machine learning, and their applications to biomedical studies. His group works closely with collaborators in the field of infectious disease, microbiome, and cancer and develop novel statistical machine learning models to address difficulties in these biomedical areas. Dr Zhu completed his PhD at UNC Chapel Hill, where he worked on developing random forest models and theories for high-dimensional and complex data. During his postdoc at Yale University, he focused on genetic and genomic analysis, and developed personalized treatment strategies using genetic data.

Drs. Holscher and Zhu’s latest collaborative publication focused on machine learning helps researchers identify bacterial biomarkers to determine food intake. They have also recently published work on estimating heterogeneous treatment effects.

What is your collaborative research in personalized nutrition about?
We are interested in understanding how the gut microbiome mediates and moderates an individual’s response to nutritional interventions. For example, we are investigating key microbes that help a person ‘respond’ to walnut consumption to lower their cholesterol? Another key focus of our work has been using microbial biomarkers to predict food intake. Since dietary records have limitations, there is a need to develop objective biomarkers of food and nutrient intake. Our work helps to fill this need.

How did you learn about each other’s research and how did you start collaborating?
We met back in 2016 when we were both new assistant professors looking for collaboration opportunities. At that time, we were both just starting to collaborate with Colleen Bushell at the Illinois Research Park (Colleen and her team have now joined NCSA) for data analytic problems. So, Hannah brought a microbiome problem to Colleen, and Colleen thought Ruoqing would fit that project well with his statistical expertise. And the three research teams have been collaborating ever since.

How are you conducting your collaborative research in personalized nutrition?
Hannah and her research team conduct nutrition intervention studies where they collect biological and behavioral data from participants participating in feeding studies. Key measures in these studies include microbiome and metabolome data as well as a range of health status measures. When all the data are integrated, the data structure is complex. Also, many of the studies use different designs, like crossover vs. parallel arm designs, which require additional considerations. We have weekly meetings to discuss the analysis plan of these data and develop new approaches that could address various statistical issues such as overfitting, confounding, batch effects, etc.

What do you do to continue grow your collaborative research relationship?
We have consistent meetings and discussions to generate new ideas and approaches to solve research problems we are both interested in. Our NCSA faculty fellowships also played a key role in supporting our collaborative efforts. Most recently, we’ve been focusing our efforts on writing manuscripts and submitting grants together to continue to support our collaborative research.

What are some challenges with collaborating across disciplines and what have you found to be effective at building a stronger and productive collaboration?
Ruoqing: For me, understanding the data collection procedures and the background biology was a big part of the challenge. Same as any collaboration, it requires literature reading to understand the concepts, terminology, thought processes and concerns from the biological side to come up with meaningful statistical approaches.
Hannah: One of the major hurdles is communication. The same term can be used differently across fields, and that causes confusion. Building a strong and productive collaboration requires open communication and a willingness to keep asking questions. Our collaboration has made everyone on the team better because we are challenged to think of different ways to explain our science and where we want to go next in terms that are understandable to experts outside our field of study.

How do you think that being a part of the Personalized Nutrition Initiative community will support and enhance your research?
Ruoqing: My main research area is personalized medicine. The methods that have been traditionally developed and used in pharmaceutical research can also be applied to personalized nutrition. However, there are also new challenges because nutrition and food intake can have a much greater variability and it is also a long-term process rather than taking drugs, which is done in a short period of time. This requires new theoretical and methodological development in statistics and machine learning. Being involved in the personalized nutrition initiative, I have the chance to communicate with leading experts in this area and understand the practical need in this field. This will motivate my own statistical research and have the chance to apply them in real applications.
Hannah: I am very excited that the Personalized Nutrition Initiative is establishing a community of researchers with complementary skills and interests. Getting the group together to talk about their science and how it could be applied across fields will help spur new ideas that can be undertaken together. I have already learned so much from the group by working together this past spring to submit an NIH grant proposal. I am looking forward to future networking events and funding opportunities that will help move the field of personalized nutrition forward.

What is the long-term goal of your research in this area?
We are working with an interdisciplinary team of researchers across campus through the Personalized Nutrition Initiative on grant proposals in the area of personalized nutrition for precision health, this work is co-led by Drs. Sharon Donovan and Saurabh Sinha. There are many new ideas involved, such as new data collecting strategies and applying some of our recently developed analysis tools. For example, we are looking forward to expanding our analytic approaches to better understand how the microbiome can be leveraged to help predict nutrient intake and personalized health trajectories.

Do you have a personal story to share or path that led to your interest in this area of study?
Ruoqing: Back to when we were still at the Research Park (it was probably our first meeting), I asked Hannah why broccoli is related to cancer incidence. She explained to me that, because humans cannot directly digest some of the substances in broccoli, we rely on enzymes from some bacteria to break down these ingredients (glucosinolates, I still cannot pronounce many of these fancy words) for us. And during that process, chemical compounds are produced, which were found to be associated with reduced cancer incidence. That “host-microbe interaction” was quite an interesting dynamic to me, so I got interested in this area.
Hannah: Learning about the microbiome during graduate school and my postdoctoral training inspired me to think more holistically about nutrition. I found topics on microbial ecology and host-microbe interactions to be fascinating. This spurred my interest in approaching nutrition problems from a more systematic level instead of focusing on just one nutrient or just one health outcome. This has been rewarding because it’s allowed me to build great collaborations and friendships with scientists across disciplines.

[published in the July 2021 Newsletter]

Zeynep Madak-Erdogan, PhD, is an Associate Professor in the Department of Food Science and Human Nutrition, Health Innovation Professor of College of Medicine, and the Director of the Women’s Health and Nutrition Lab. She also has affiliate appointments with the Division of Nutritional Sciences, the Institute of Genomic Biology (IGB), the National Center for Supercomputing Application (NCSA), the Cancer Center at Illinois, the Center for Digital Agriculture, and the Beckman Institute. Through her research, she seeks to improve the quality of life for women and breast cancer survivors by understanding the link between hormones and metabolism. Her lab uses multiscale modeling of –omics data from patient samples, animal models, and an engineered in vitro tumor models to understand the molecular basis of the crosstalk between metabolic regulation and nuclear receptors. She has received several awards including the Women in Endocrinology Young Investigator Award from Endocrine Society and the Mary Swartz Rose Young Investigator Award and the Bioserv Experimental Nutrition Award from American Society of Nutrition.

Colleen Bushell, MFA, is the Director of the Healthcare Innovation Program and a research scientist at the NCSA. She has affiliate positions with the Carle Illinois College of Medicine, and in IGB’s Genomic Security and Privacy theme. Her work is in the area of visual analytics, specifically visualization design and software user interface development for communicating complex information. She was an early pioneer in the field of data visualization, addressing challenges in multiple scientific and engineering fields for more than 30 years including Mosaic: the first web browser. She focuses on converting complex data into meaningful visuals and interactive workflows that help people understand information. In her current role, she facilitates collaborative efforts in the health domain that require NCSA’s expertise in data science — especially analytics, visualization, software development, cybersecurity and advanced computation.

Zeynep and Colleen’s latest collaborative publication focused on early liver toxicity gene biomarkers using comparative supervised machine learning. They have also recently published work on long-term estrogen supplementation effect on gut microbiota and microbial activity.

What is your collaborative research about? 
We have worked on many projects over the years where our team’s role focuses on data analysis and the development of new software workflows and visualization tools. Our collaboration spans projects related to liver health and long-term broccoli feeding, identification of metabolites and cytokines related to increased breast cancer risk, identification of biomarkers of liver toxicity, and more recently genomic analysis of metastatic breast tumors.

How did you learn about each other’s research and how did you start collaborating?
Zeynep: Our first interaction goes back to 2016. At that time, we were working on a project related to liver health benefits of long-term broccoli feeding. I remember our first meeting, when Colleen and her team members presented what they do. I was blown away and I really wanted to collaborate with her group to analyze and visualize our data from various projects.
Colleen: We were connected with Zeynep through one of my collaborators. We kicked-off our first effort through a proposal to College of ACES for internal seed funding. I was very impressed by her research and it wasn’t long before I learned she is full of great ideas and works hard to create collaborative teams to reach her goals.

How are you conducting your collaborative research?
It requires a lot of discussion about the research questions, the data, the analytical approaches, and the results. It’s always an iterative process and requires on-going, close collaboration between the data scientists, the nutritionist, and the students. We mostly work together through regular meetings, twice weekly to monthly. Zeynep will be on sabbatical at NCSA during Spring 2022. She is very excited that she will be physically at NCSA where she can interact more with Colleen’s group.

What do you do to continue growing your collaborative research relationship?
Main drivers are various grant proposals that we submit together. We have collaborated on many proposals and often participate in similar research activities across campus that introduces us to new opportunities.

What are some challenges with collaborating across disciplines and what have you found to be effective at building a stronger and productive collaboration?
The initial challenge is learning what everyone’s expertise is and how each person can contribute to the project. We have to learn enough about each other’s domain to have meaningful discussions, but we can’t each become experts in all areas. So, there needs to be a friendly, respectful environment for building effective collaborations. We have been successful in doing this. The biggest challenge is always funding. Since we at NCSA are entirely soft-funded we must find funding for every activity. Seed grants, such as NCSA’s Fellows program or Cancer Center’s seed grant program, are great for developing new relationships and new projects, but then long-term funding is always needed to sustain the collaboration.

How do you think that being a part of the Personalized Nutrition Initiative community will support and enhance your research?
Zeynep: As mentioned above, these programs and initiatives are critical incubators for collaboration. I am very hopeful that Personalized Nutrition Initiative will enable us to continue our productive collaboration and ensure more research publications and funding.
Colleen: I think there are a lot of diverse skills and interests in the Personalized Nutrition Initiative. Bringing these together to tackle the difficult research questions or to overcome barriers that hinder research is important. Through the Personalized Nutrition Initiative, I will learn how I, and NCSA in general, can contribute to the community.

What is the long-term goal of your research in this area?
Zeynep: We still lack universal biomarkers for certain metabolic diseases such as gestational diabetes, coronary microvascular disease, and certain subtypes of breast cancer in health disparate populations. We would love to extend our datasets and employ more visualization tools that Colleen’s group develop. Our long-term goal is to reduce barrier to early diagnosis of chronic disease by employing these novel biomarkers and visualization tools and reduce mortality and morbidity due to cancer, cardiovascular disease, and diabetes in health disparity populations.
Colleen: I hope to facilitate the development of software tools and cyber-environments for conducting powerful and efficient analysis of data — tools that encapsulate successful analytical and visual techniques – like those we developed for Zeynep’s studies – so they can be confidently used by many nutrition scientists. Right now, it is too labor intensive for researchers to pursue answers to all the questions they know they can derive from their data.

Do you have a personal story to share or path that led to your interest in this area of study?
Zeynep: I knew I wanted to be a researcher since I was in middle school. I am very lucky to be at this campus and collaborate with amazing people like Colleen. I am excited about Personalized Nutrition Initiative where more such fruitful interactions will be established.
Colleen: I have spent my career designing ways to represent complex data in many scientific domains, but I have focused on health and nutrition over the last 10 years. This interest stems from two of my kids who developed type-one diabetes, and their relentless need to monitor, measure and analyze everything they eat, every day, without any break – ever. And especially, for all three of my children, how their food choices affect their physical and mental health short-term and long-term. Helping to understand better how nutrition and toxins might affect the development and outcome of auto-immune diseases and cancers is a personal goal of mine and one of the many reasons I have enjoyed working with Zeynep all of these years.

[published in the September 2021 Newsletter]