Summary: Researchers have discovered a surprising link between immune cells in the gut and brain in Alzheimer’s disease. In mice, antibody-producing B cells, which are normally found in the intestines, were seen to migrate to border regions of the brain, influenced by chemokine signals from pro-inflammatory brain cells.
Feeding animals a high-fiber diet restored immune balance in the gut and reduced symptoms of dementia, even without reducing plaque concentrations. The findings suggest that the gut-immune-brain axis may be an important target for new Alzheimer’s treatments and interventions for healthy aging.
Key facts
- Immune migration: B cells from the gut have been found in the brains of Alzheimer’s patients, which are controlled by chemokines.
- Effect on food: Fiber-rich inulin restored immune balance in the intestines and reduced weakness.
- Increased healthy life expectancy: Fiber did not reduce plaque, but improved quality of life in the mouse model.
Source: Buck Institute
The intestines contain the largest collection of immune cells in the body.
New research from the Buck Institute shows that some of these immune cells migrate along the gut-brain axis in a mouse model of Alzheimer’s disease, potentially offering a new treatment option for the memory-destroying disease.
A study published in the August 29, 2025, issue of Cell Reports reveals that a high-fiber diet can significantly reduce symptoms of Alzheimer’s disease in mice, including tremors. The research highlights the connection between diet and brain health, suggesting that dietary fiber may play a protective role in neurodegenerative conditions.
“This paper places the gut immune system at the forefront of the pathology of neurodegenerative diseases,” said Daniel Weiner, an associate professor, immunologist, and co-senior author of the study. The findings underscore the importance of the gut-brain connection and open new avenues for potential treatment strategies targeting the immune system through nutrition.
“Given their size and the cells’ ability to travel, it makes sense that these immune cells have the potential to affect broader physiology.”
Professor Julie Anderson, PhD, neuroscientist and co-senior author, adds: “To our knowledge, this is the most comprehensive study of the gut immune system in a neurodegenerative disease model. We hope to study its effects on other diseases such as Parkinson’s disease and multiple sclerosis.”
The study was led by postdoctoral researcher Priya Mukhijani, PhD, an immunologist and assistant professor at the Weiner & Anderson Labs. Mukhijani discovered that antibody-producing B cells, which are normally responsible for maintaining harmony between the gut microbiome and the immune system, are reduced in mice bred to develop Alzheimer’s disease.
They also discovered that this cell type has a migratory signature: the researchers found gut-specific B cells and their migratory receptors in the brain and its border region, the meningeal dura mater.
“Surprisingly, we found that immune cells at the brain border, which recognize bacteria in the gut, accumulate in the brains of people with Alzheimer’s,” said Makhijani.
Mukhijani and his team sought to understand why immune cells in the gut were depleted. They discovered that the binding partner of this immune cell receptor in the gut, a well-studied chemokine known for its translocation, is produced in higher numbers in inflammatory cells, glia, in the brains of people with AD.
The migration pattern was also identified through data mining of previous studies in human brains with AD.
Working with colleagues at the University Health Network, part of the University of Toronto, the team conducted experiments using a small molecule drug to block the brain axis. This suggests that a new, long-range mechanism is at work in the brain-gut axis.
The benefits of a high fiber diet
Mukhijani and his team found that administering the anti-inflammatory prebiotic fiber inulin restored balance in the intestines of mice with Alzheimer’s disease.
“We found that these cells that migrated into the gut were replenished, and the animals had reduced Alzheimer’s-related risks, including tremors,” explained the researcher. This suggests a direct link between immune cell activity in the gut and the progression of neurodegenerative symptoms in the brain.
He further noted that inulin—a type of dietary fiber—produces short-chain fatty acids and other metabolites concentrated in the gut, which can also circulate throughout the body. These compounds appear to play a key role in enhancing gut health and potentially influencing brain function from afar.
“The diet improved gut health and reduced chemokine signaling in the brain,” he added. “Here too, it was a two-way street,” he said, highlighting the dynamic relationship between the gut and brain. This bidirectional communication could be crucial for understanding how dietary interventions affect brain diseases like Alzheimer’s.
Weiner noted that the high-fiber diet did not permanently reduce the amount of plaque in the mice’s brains, but it did affect overall health.
“We tested these mice on 31 parameters of aging. The diet undoubtedly extended their lifespan and improved their quality of life,” he says, “This plan supports the advice to ‘eat fruits and vegetables,’ which is found in almost all dietary recommendations.”
The big picture
While this study provides a comprehensive picture of changes in the gut immune system in neurological disorders, the researchers say that more research is needed to determine whether these changes are a response to changes in the brain or whether they cause the disease itself.
According to Weiner, one possible explanation is that age-related stress may trigger AD-causing inflammation in the brain, with chemokines signaling the gut’s immune system to help deal with stress.
“Initially, this process is likely protective, but over time, the gut becomes compromised, allowing more dangerous types of bacteria to thrive and fueling inflammation throughout the body.”
Makhijani is keen to explore the possibilities of understanding and/or altering the gut microbiome in the context of disease.
Perhaps there is a microbiome that signals an increased risk of neurological disorders. Perhaps we can identify specific bacteria that cause inflammation in the immune system. What if we could block signaling chemokines early in the disease process? Would that protect the entire system? This article offers many possibilities for further research.
Other Buck collaborators include: Taylor R. Valentino, Max Manwaring-Muller, Rohini Imani, Wei Chieh Mo, Carlos Galicia-Aguirre, Anand Rane, Kenneth A. Wilson, Alexander Kafil, Hexin Du, Fei Wu, Jenny Hong-Yung, Benjamin D. Ambrose, Prasanna Vidhana, David Shumang, David Shumang, Li and Ashok. Ellerbe. Other co-authors include Christopher Ryan Tan, Saad Khan, Chao Wang, Arthur Murtha and Olga L. Rojas, Department of Immunology, University of Toronto, Toronto, Canada; Nan Chen, Department of Cellular and Molecular Biology, Toronto General Hospital Research Institute, Toronto, Canada; and Sean Weiner, Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Canada.
About this Alzheimer’s disease research news
Author: Kris Rebillot
Source: Buck Institute
Contact: Kris Rebillot – Buck Institute
Image: The image is credited to StackZone Neuro
Original Research: The findings will appear in Cell Reports
Funding:
The work was supported by NIH grants 3RF: AG062280-01S1, NIA T32 AG000266, AG066591, PO1AG06659.
COI disclosure: Daniel Weiner is the co-founder of Proprion Inc., a company that researches interventions involving the gut immune system and related metabolites in aging and related diseases.
