How Diet Interacts with the Gut

The 14th Iva Dostanic lectureship took place on Thursday, June 20, 2024 with Lisa Korn, MD, PhD, instructor of medicine (rheumatology, allergy and immunology), presenting her research findings on diet-immune interactions.

Korn was selected as the 2024 Iva Dostanic, MD, PhD, Physician-Scientist Trainee Award recipient. The award is named in memory of Dostanic, a former trainee who passed away from ovarian cancer in 2011 at the age of 35.

Peter S. Aronson, MD, C.N.H. Long Professor of Medicine (Nephrology), welcomed those who sat in the Fitkin Auditorium and gave a background on Dostanic, her journey to Yale, and the profound impact she had on others.

Dostanic’s accomplishments and accolades are noteworthy. She graduated from Manhattanville College with multiple awards and honors, and then attended University of Cincinnati College of Medicine for her PhD degree in molecular genetics, biochemistry, and microbiology. It was there that she first-authored five papers – each garnering over 100 citations. Although she could have obtained a faculty position in a basic science department, she aspired to also be a physician, so she attended the Cleveland Clinic Lerner College of Medicine.

After medical school, she was recruited to the ABIM Physician-Scientist Research Pathway in the Traditional Internal Medicine Residency Program in the Department of Internal Medicine at Yale School of Medicine.

Aronson described Dostanic as a “true force of nature” and how she had great passion and love for both science and medicine. “Iva was hardly a stereotypical science nerd. Indeed, Iva brought passion, energy, elegance, playfulness, humor, and joy to all aspects of her life.”

He recalled how, during the final weeks of her life, Dostanic dismissed her ailments when visitors came to her bedside at Yale New Haven Hospital. Instead, she glowed as she described her exciting pulmonary research ideas.

Because Iva’s passion, commitment and optimism despite all odds represented the very ideal of what it means to be a physician-scientist, the department established an annual award and lecture in her name.

“Iva’s parents, Predrag and Dragana Dostanic, annually make a special trip to New Haven to attend the award presentation and lecture and to meet the awardees personally. Moreover, the Dostanics have become devoted friends of Yale, and established an endowed fund in Iva’s name to support physician-scientist career development in the Department of Internal Medicine,” said Aronson.

In concluding his background on Dostanic, Aronson shared an uplifting message for the audience, “In addition to recognizing outstanding trainees like today’s awardee, Lisa Korn, we have another goal in telling Iva’s story on this occasion. For all the students, residents, and trainees in the audience today, our hope is that you will be inspired by Iva’s love for science and medicine and especially by the enormous joy she found in work right up until her last days. And we hope that imbued with Iva’s spirit, each of you will also find joy and fulfillment as you apply your own special gifts and talents to advance the science, or practice, or teaching of medicine.”

Introducing Awardee Lisa Korn, MD, PhD

Richard Bucala, MD, PhD, Waldemar Von Zedtwitz Professor of Medicine (Rheumatology), professor of pathology and of epidemiology, and section chief of rheumatology, allergy, and immunology, spoke about Korn’s education and training.

Just like Dostanic, Korn came to Yale through the ABIM Physician-Scientist Research Pathway, and ultimately joined as an instructor in the section in 2022.

“As her division chief, I can say that our faculty could not have been more pleased that Lisa selected rheumatology,” said Bucala. “Lisa is an outstanding physician, by all accounts from her residency and fellowship training here at Yale. This adds immeasurably to her scientific potential by allowing her to identify relevant questions in the context of natural variation among individuals to provide a greater understanding of disease.”

Diet-immune Interactions

Diet is relatively newer in the medical field. Because the best diets for patients with inflammatory and autoimmune diseases is not well understood, it is considered an unmet need in rheumatology, says Korn.

“When our patients come into the clinic and ask what to eat, we don’t really know what to tell them,” Korn admits. “The study of diet has been rapidly changing over the last 100 years or so. It wasn’t until around 20 years ago or so that we started to consider complex dietary patterns as the way to think about diet.”

Diet is one of many environmental factors that is involved in disease flares, and Korn has been most interested in exploring diet and its role in systemic disease states and how it interacts with the immune system.

In her presentation, she discussed how the intestine senses and responds to various environmental factors, such as stress, diet, infection, and injury. Other factors that influence intestinal responses are the time of day and the microbiota.

The intestine is a tissue that contains resident cells with tissue specific functions, such as monitoring against invasion and defending the intestinal barrier. Dietary constituents interact with these specialized immune cells to influence both local and systemic responses.

Korn and team studied the impact of various diets on the gut. They created four different diets in partnership with a nutritionist, and they discovered that a high-protein diet reduces the presence of a particular immune cell type called the eosinophil.

“The most striking thing that we found when we looked at all the immune cells was that a high-protein diet–and only the high-protein diet–caused about a two-fold reduction in intestinal eosinophils. I wasn’t expecting to become an ‘eosinophil person’ when I started these studies,” she jokes.

The role of eosinophil in the gut is not well known, but they can make-up over twenty percent of immune cells in parts of the small intestine. These studies show that dietary protein regulates eosinophil adaptation to the small intestine.

While there is much more to learn, ultimately Korn and team note that eosinophil adaptation to the small intensive involves changes in multiple gene expression programs.

“What seems like a relatively minor dietary change generates [a] unique set of gene expression signatures. It’s interesting to think about how this could interact with the intestine, and intestinal immunity in particular.”

Looking ahead, Korn wants to explore how diet impacts other parts of the body.

“There are many questions left to answer. We don’t know how these dietary changes are coordinated across tissues. The gut immune cells are in communication with many different organs in the body,[ which happens in part by] immune cell trafficking.”

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