Brain food: Freeman’s research looks at link between microbiome and immune cells

In February, Linnea Freeman, associate professor of biology and neuroscience, flew to Salt Lake City and spent three days at the University of Utah in immunologist Gianna Hammer’s lab. There, Freeman tested young and old mice with symptoms of colitis for anxiety and sociability, and recorded teaching videos so Hammer’s researchers could learn to do these behavioral tests on the animals, too.

The goal of this cross-country collaboration is to better understand how age, the bacteria that populate the mouse gut, and immune cells intersect. The work was funded by a grant of $55,000 each to Freeman, Hammer and Lisa Osborne, an associate professor at the University of British Columbia. The scientists won the award during the second year of a three-year “Scialog” fellowship in Microbiome, Neurobiology and Disease through the Research Corporation for Science Advancement (RCSA). As an RCSA Scialog fellow, Freeman and 50 other early career faculty gathered three times—both virtually and in person—to discuss the big questions of the brain and gut, a little bit “like a think tank,” she said.

The project Hammer and Freeman hatched at Scialog continued this summer, looping in three Furman undergraduate researchers. The folks in the Hammer lab maintained the mouse model, conducted immunology experiments and recorded videos of the behavioral tests Freeman taught them to do on the mice. One of Freeman’s students analyzed them.

Freeman’s group also took delivery of mouse brains from Utah. They sliced this neural tissue thinner than paper, then used a technique to visualize the main immune cells of the brain, called microglia, under a microscope. By looking at differences in the number and location of microglia present in the mouse brains and how the young and old mice with and without colitis symptoms behave, the team can explore how age and gut inflammation affect inflammation in the nervous system and subsequent behavior.

“What excites me the most about neuroscience is the uncharted territory,” Freeman said. “Our brains control everything, but there’s so much that we don’t know about. I feel like I’ll never be out of a job.”

To this end, Freeman has other projects in the works exploring the connections between the gut microbiome and the brain. In 2022, she was awarded an $8,500 Bioinformatics Pilot Project Program grant from the South Carolina IDeA Networks of Biomedical Research Excellence for work to assess the makeup of the gut bacterial communities in a mouse model of autism. And on August 17, Freeman earned an R15 grant from the National Institutes of Health to study the sex differences in the gut microbiome and how they influence consumption of a high fat diet in rats.

Freeman’s project “on the harmful effects of consuming a high fat diet is of great importance,” according to Matthew Carter, an associate professor of biology at Williams College in Massachusetts. “Her work has shown that diets high in saturated fat can cause inflammation in the brain and changes to the blood-brain-barrier, consequential findings that inform health and disease,” he adds.

One of the health implications that Freeman has incorporated into both the autism and high fat diet studies is exploring biological sex differences. “A passion of mine is understanding how males and females differ,” she said. Increasing that understanding could pave the way for incorporating variations between the sexes into personalized medicine.

While each of these projects have pursued some aspect of a microbiome and nervous system connection, they’ve also relied on connections and community both within and beyond Furman to be successful. A big part of that community is the students. “I’m grateful for the work that the undergraduate students put in. I love that part of my job,” Freeman said. “It’s cheesy, but they’re the future of the medical field as well as basic science.”

One of those young scientists, Emma Bondy ’20, worked in the Freeman lab from summer 2019 until her graduation from Furman in 2020. “I learned so many techniques—immunohistochemistry, microscopy (brightfield and fluorescence), software,” Bondy, who is now pursuing a doctorate at the University of Kentucky, said.

“But more importantly … Linnea also taught me some really important lessons: how to respond after making a mistake, how to stay patient when the work starts to feel tedious, how to balance work with personal life, and how to build strong collaborations.”