Stephanie Peterson successfully defends and publishes her Ph.D. Thesis

Dr. Ashutosh Mangalam and Stephanie PetersonStephanie Peterson successfully defended her PhD thesis in early October and completed the Immunology PhD program. Stephanie’s thesis is entitled A tale of two diets: Divergent effects of fructose and isoflavones in a mouse model of Multiple Sclerosis. She performed her thesis work in the laboratory of Dr. Ashutosh Mangalam where she examined the effects of fructose on the gut microbiome, immune system, and disease outcomes in a mouse model of Multiple Sclerosis. Additionally, Stephanie investigated potential mechanisms of isoflavone-mediated protection in these mouse models.

Multiple Sclerosis (MS) is a debilitating disease of the brain and spinal cord affecting an estimated 2.8 million people worldwide. Diet has emerged as a major environmental factor because compounds in food can interact with the gut microbiome, changing the bacteria and their functions to either benefit or harm the host. Western-style diets high in fat, sugar, and processed foods are associated with various negative health outcomes, while diets rich in plants and fiber are generally more beneficial. Additionally, “developed” countries such as the USA, Canada, and many areas of Europe where a Western diet is the norm are also the areas with the most people diagnosed with MS. Thus, we investigated the effects of two dietary components with potentially opposite effects: fructose and isoflavones. Fructose is a sugar found in high quantities in the Western-style diet and we hypothesized that it would negatively affect the gut microbiome and disease outcomes in an animal model of MS. Conversely, isoflavones are plant-based estrogenic compounds with the ability to reduce symptom severity in an MS animal model, but the mechanism of that protection is not well understood. We hypothesized that isoflavones reduce MS severity through estrogen receptor signaling, especially on CD8+ T-cells. We found that fructose can alter the gut microbiome and its’ function, as well as the immune response. Despite these changes, a fructose rich diet did not translate to worse clinical outcomes in the animal model of MS. Furthermore, even when fructose was given in combination with a high fat diet, making it closer to the Western diet, it had no significant effect on disease outcome. Additionally, when investigating how isoflavones provide protection in MS, it was found that CD8+ T-cells in the colons of isoflavone-fed mice had altered properties compared to isoflavone-free fed mice. Overall, my data show that fructose and isoflavones have different effects on the host immune response and disease. A better understanding of these varied effects will help us identify targets for future therapies or find compounds that patients with MS should potentially avoid to slow or stop disease progression.

Importantly, the fructose section of Stephanie’s thesis was recently published in the journal ImmunoHorizons. The paper can be viewed at:

Monday, October 23, 2023