Alzheimer’s disease has long been seen as a brain problem—an illness of tangled proteins, plaques, and dying neurons. But what if part of the answer lies not in the brain alone, but deep within the gut?
New research from the Buck Institute for Research on Aging suggests just that. In a groundbreaking study using a mouse model of Alzheimer’s, scientists discovered that immune cells from the gut travel along the brain–gut axis, potentially influencing the course of the disease. The findings open a promising new window into how Alzheimer’s develops—and how diet and immunity might help slow its devastating toll.
The Gut: The Body’s Largest Immune Hub
The gut isn’t just a digestive organ—it’s also home to the largest population of immune cells in the body. These cells constantly communicate with the trillions of microbes that make up the gut microbiome, striking a delicate balance between defense and harmony.
Dr. Daniel Winer, an immunologist and co-senior author of the study, explains: “Given its size and the cells’ ability to travel, it makes sense that those immune cells would have the ability to influence larger physiology.”
For years, scientists suspected that the gut might influence brain health through what’s called the brain–gut axis. This new research offers some of the strongest evidence yet: immune cells from the gut not only move into the brain but also appear to play a role in Alzheimer’s pathology.
A Surprising Journey: Gut Cells Found in the Brain
The research team, led by postdoctoral fellow Dr. Priya Makhijani, focused on antibody-producing B cells—special immune cells normally responsible for keeping the microbiome in check. In mice bred to develop Alzheimer’s, these B cells were drastically reduced in the gut.
But they weren’t disappearing. Instead, they were traveling.
Makhijani and her colleagues found these gut-derived B cells inside the brain’s protective border region, the meningeal dura mater. Even more astonishing, the cells seemed to recognize bacteria from the intestines, suggesting they were carrying gut “memories” into the brain.
“Remarkably, we found that these immune cells in the brain border which recognize bacteria living in the intestines were accumulating in the AD brain,” Makhijani explains.
This discovery suggests a new mechanism in which the inflamed brain may “call for help” from the gut, drawing immune cells across the body’s most protected boundary.
Why the Cells Migrate
What drives these immune cells to leave their home in the gut? The team found that a signaling molecule—known as a chemokine—was produced at high levels in the Alzheimer’s brain. This chemical beacon acted like a magnet, pulling gut immune cells toward the site of brain inflammation.
Intriguingly, the same migratory signature was also found in data from human Alzheimer’s brains, suggesting this isn’t just a mouse phenomenon.
When researchers tried blocking this signaling pathway with a small-molecule drug, they were able to interfere with the migration process—hinting at potential therapeutic strategies to modulate this long-range immune response.
The Healing Power of Fiber
One of the most striking findings of the study was how diet shaped the gut–brain connection. When Alzheimer’s-model mice were fed inulin, a prebiotic fiber found in foods like chicory root, garlic, and onions, their gut balance was restored.
The high-fiber diet replenished the gut’s immune cells, reduced brain inflammation, and even lessened frailty symptoms, such as tremors.
“We found these migrating cells were replenished in the gut and that AD-related frailty, including the tremor trait, was reduced in the animals,” says Makhijani.
Although fiber didn’t consistently shrink Alzheimer’s plaques in the brain, it clearly improved overall health and quality of life. Dr. Winer highlights that in tests measuring 31 different aspects of aging, the fiber-fed mice fared significantly better. “The diet definitely extended their health span, giving the animals a better quality of life,” he notes.
In other words, while fiber might not be a cure for Alzheimer’s, it could help slow its impact—offering patients more years of healthier living.
Bigger Implications: Beyond Alzheimer’s
This study is not just about one disease. If gut immune cells can influence Alzheimer’s, they may also play a role in other neurological conditions like Parkinson’s and multiple sclerosis.
Buck professor and co-senior author Dr. Julie Andersen emphasizes the broader significance: “As far as we know, this is the deepest investigation of the gut immune system in a model of neurodegenerative disease. We look forward to studying its impact in other diseases.”
If confirmed in humans, this work could redefine how scientists think about the origins of brain disorders—shifting attention from neurons alone to the gut, the microbiome, and the immune system that links them together.
A Delicate Balance Between Protection and Harm
The researchers propose that the gut-to-brain immune migration may start as a protective process. In early stages of disease or aging, the brain might send distress signals to recruit help from the gut. But over time, as the gut immune system becomes compromised, harmful bacteria may flourish, driving chronic inflammation that worsens brain decline.
“In the beginning, the process is likely protective,” Winer suggests, “but over time the gut becomes compromised, setting the stage for more dangerous types of bacteria to flourish which fuels inflammation throughout the body.”
This dynamic balance—between defense and destruction—may help explain why neurodegenerative diseases are so difficult to treat.
The Road Ahead
For Makhijani and her team, the next step is to dive deeper into the microbiome itself. Could certain bacterial species predict risk for neurological disease? Could altering the microbiome early in life protect the brain later on?
“Maybe there is a microbiome that signals an increased risk of neurological disease,” Makhijani says. “Perhaps we’ll be able to identify specific bacteria that set off immune system inflammation. What if we can inhibit the signaling chemokines early versus late in the disease process? Which would be protective for the whole system?”
These are questions with profound implications—not just for Alzheimer’s, but for the future of medicine itself.
Hope in the Microbiome
The findings from the Buck Institute remind us that the human body is not a collection of isolated organs but a dynamic, interconnected ecosystem. The gut, often overlooked in neurological research, may hold vital keys to protecting the brain.
For patients and families living with Alzheimer’s, the prospect of new therapies born from something as simple as diet is deeply hopeful. While much more research is needed before these discoveries translate into treatments for humans, the message is clear: the road to brain health may begin in the gut.
And sometimes, the smallest changes—like eating more fiber—can be powerful acts of prevention and healing.
More information: Amyloid-β driven Alzheimer’s disease reshapes the colonic immune system in mice, Cell Reports (2025). DOI: 10.1016/j.celrep.2025.116109. www.cell.com/cell-reports/full … 2211-1247(25)00880-0
