College of Agriculture & Natural Resources Department of Food Science and Human Nutrition

Newly published research by Michigan State University (MSU) researcher James Pestka explores how simple dietary modifications can help manage autoimmune diseases, aiming to improve patient care and quality of life.

Pestka, the Robert and Carol Deibel Family Endowed Professor and University Distinguished Professor with dual appointments in the Department of Microbiology, Genetics, & Immunology and Department of Food Science and Human Nutrition, has long explored the intricacies of autoimmunity. His work primarily focuses on understanding the complex relationship between environmental factors, diet and autoimmune diseases.

According to the National Institutes of Health, approximately 8 percent of the U.S. population suffers from an autoimmune disease. These diseases, chronic and debilitating, can occur at any point across one's lifespan and have no known cure. Despite their significant prevalence, many autoimmune diseases are understudied, and treatment options are limited, often coming with serious side effects and high costs.

The new research, published in Frontiers in Immunology, “Serum Fatty Acid Profiles in Systemic Lupus Erythematosus and Patient Reported Outcomes: The Michigan Lupus Epidemiology & Surveillance (MILES) Program,” is a collaboration with Emily Somers, a professor at the University of Michigan Schools of Medicine & Public Health, and Jenifer Fenton, a professor in the Department of Food Science and Human Nutrition, that builds on Pestka’s ongoing work to understand how dietary modifications can help prevent environmental toxicants from triggering lupus.

Lupus is an autoimmune disorder in which the immune system attacks healthy cells and tissues, resulting in inflammation and, in some cases, permanent tissue damage. The disease can affect numerous body parts, including the skin, heart, lungs, kidneys and brain.

While the cause of lupus is unknown, genetics and environmental factors play a significant role in disease onset and progression. Exposure to toxic substances, such as crystalline silica, the most abundant mineral on earth and a component of dust and pollution, has been linked to an increased risk of triggering lupus and other autoimmune diseases.

One key area of Pestka’s research focuses on those with lupus nephritis, a severe condition in which inflammation leads to changes in kidney function, including kidney failure. Current management strategies for lupus nephritis include the use of immunosuppressive drugs and steroids, which, while effective, cause serious side effects such as infections, organ damage and bone loss.

Pestka hopes to build on previous studies that have shown promise in a safer, cost-effective treatment to maintain kidney health, prolong remission and prevent relapse of lupus nephritis — the source: omega-3 fatty acids, which are produced in marine algae and concentrated in cold-water fish.

Omega-3 fatty acids, particularly docosahexaenoic acid (DHA) found in fish oil, are known for their anti-inflammatory properties and have shown remarkable potential in reducing inflammation resulting from lupus.

Pestka’s team has also demonstrated that these nutrients can significantly impact lupus progression. For instance, exposure to silica triggers accelerated lupus in genetically predisposed mice, causing the disease to develop much earlier. However, supplementing the mice’s diet with omega-3 fatty acids has led to various benefits, including mitigation of inflammatory damage, improved health outcomes and even prevention of early-onset lupus.

“For the last 15 years, we have been studying how occupational exposure to toxicants can trigger autoimmunity in a mouse model,” said Pestka. “We're looking at how consumption of omega-3 fatty acids can impact the development of lupus. We've successfully shown that we can trigger accelerated lupus nephritis in lupus-prone mice, which develops three months earlier, and then we can prevent that by feeding omega-3 fatty acids.”

A unique aspect of Pestka’s studies is the exclusive use of the omega-3 DHA produced from algal cultures — a sustainable source. In this new research, he and his collaborators report that blood DHA concentrations are associated with improved patient-reported outcomes on disease activity, pain and sleep quality in individuals with lupus. On the other hand, blood levels of saturated, monounsaturated and fatty acids — the primary fats in ultraprocessed foods — are associated with adverse outcomes.

Supplementing omega-3s, either singularly or in combination with smaller doses of immunosuppressive drugs, could help patients avoid the harsh side effects of current treatments while reducing the likelihood of ongoing flare-ups by addressing the existing limitations of current therapies. There is hope that by advancing the understanding of how omega-3s influence the progress of lupus nephritis, this research could potentially lead to new prevention and treatment strategies for the broader lupus disease.

“We believe that consuming more omega-3 fatty acids through diet or supplements, could be a way to lessen various inflammatory and autoimmune diseases,” said Pestka. “Our idea is to include omega-3s in conjunction with induction therapy — when lupus nephritis occurs — and afterward, with the hope of being able to speed up patients going into maintenance, lower the doses of drugs for maintenance therapy or even eliminate their use. Our goal is to help patients avoid the harsh side effects of current drugs while reducing the likelihood of flare-ups and improving quality of life.”

Other key collaborators on this research include Andrew Olive, associate professor in the Department of Microbiology, Genetics, & Immunology; Jack Harkema, University Distinguished Professor and director of the Laboratory for Environmental & Toxicologic Pathology; and Rance Nault, assistant professor in the Department of Pharmacology and Toxicology.