Apr 09, 2026
3 min read
A new study reveals that gut bacteria may play a key role in causing ALS and frontotemporal dementia.The harmful sugars produced by these microbes can trigger immune responses that damage the brain.This finding explains why some people at genetic risk develop the disease while others do not.Even more promising, cutting back on these sugars improved brain health in experiments, suggesting new treatment options.
Scientists discover secret gut factors behind ALS and dementia
The culprit hiding in the gut can be the culprit of devastating brain diseases, and scientists have found a way to combat it.
- April 9, 2026
- Case Western Reserve University
- Gut bacteria play an important role in the development of ALS and frontotemporal dementia, according to a new study.Harmful sugars produced by these microbes trigger an immune response that damages the brain.The breakthrough could explain why some genetically vulnerable people develop the disease and why others don't.More promisingly, reducing these sugars improved brain health in trials, hinting at the possibility of a new treatment.
Researchers at Case Western Reserve University have discovered a discovery that could change the way doctors approach two of the most devastating brain diseases.Their work reveals an unexpected player in the progression of the disease: intestinal bacteria.
The team found a clear link between microbes in the digestive system and the brain damage seen in amyotrophic lateral sclerosis (ALS) and fronto-amerobic dementia (FTD).They discovered that certain bacterial sugars can trigger immune responses that kill brain cells and, more importantly, discovered ways to stop this process.
Effects of ALS and FTD on the brain
FTD mainly affects the frontal and temporal lobes of the brain, causing changes in personality, behavior and language.ALS, on the other hand, targets the motor neurons, causing muscle weakness that eventually leads to paralysis.
The underlying causes of both diseases are still not fully understood.Scientists have examined a wide range of possible factors, including genetics, environmental exposures, brain damage, and diet.
The gut-brain system defines disease risk
The research, published in Cell Reports, helps answer long-standing questions about why some people develop these diseases while others do not.Researchers have discovered a molecular mechanism that links bowel function to brain damage, especially in people with certain genetic mutations.
"We found that harmful gut bacteria produce inflammatory forms of glycogen (a type of sugar), and these immune responses to bacterial sugars that damage the brain," said Aaron Burberry, assistant professor in the Department of Pathology at Case Western Reserve School of Medicine.
Of the 23 ALS/FTD patients studied, 70% had high levels of this harmful glycogen.In contrast, only a third of people without these diseases showed similar levels.
New targeted therapies and hope for patients
These results may have immediate clinical implications.Having identified harmful sugars in the gut as the cause of the disease, researchers now have new targets for treatment.The study also highlights potential biomarkers that could help doctors identify patients who may benefit from gut-targeted therapies.
The findings open the door to new treatments aimed at breaking down these harmful sugars in the digestive system.They also support the development of promising drugs that affect the connection between the gut and the brain, slowing or preventing disease progression.
Alex Rodriguez-Palacios, an assistant professor at the School of Medicine's Digestive Health Research Institute, said the team was able to reduce these harmful sugars in their experiments, which "improved brain health and extended lifespan."
Why some carriers of the gene develop diseases
This discovery is especially important for people with the C90RF72 mutation, the most common genetic cause of ALS and FTD.Not everyone with this mutation develops the disease, and this research helps explain why.
These findings suggest that gut bacteria may act as an environmental trigger for disease in susceptible individuals.
Unique research methods made progress possible
This research was made possible by advanced experimental techniques at the Institute of Pathology and Digestive Health of the university. The scientists used a germ-free mouse model that was kept in completely germ-free conditions without the presence of bacteria. This approach allows researchers to isolate the influence of specific microorganisms on disease.
The program is directed by Fabio Cominelli, a distinguished university professor and director of the Digestive Health Research Institute.It is based on the innovative "cage-within-a-cage" sterile containment system developed by Rodriguez-Palacios, a rare capability that made this study possible.
This setup allows for large-scale studies of the microbiome, in order to examine how the gut and brain communicate.Traditional methods usually limit researchers to studying only a few animals at a time.
Next steps and clinical trials
"To understand when and why harmful microbial glycogen is produced, the team will then conduct large-scale studies examining the gut microbiome communities in ALS/FTD patients before and after the onset of the disease," Burberry said.
Content provided by Case Western Reserve University. Note: Content may be edited for style and length.
– Blake McCourt, Katelyn Lemr, Shinjon Chakrabarti, Elizabeth Woidke, Sara Ramaiah, Vaidhvi Singh, Naseer Sangwan, J. Mark Brown, Fabio Cominelli, Alex Rodriguez-Palacios, Aaron Burberry.C9orf72 in myeloid cells prevents an inflammatory response to microbial glycogen.Cell Reports, 2026;45 (2): 116906 DOI:10.1016/j.celrep.2025.116906
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