Researchers at Case Western Reserve University have discovered that toxic sugars produced by gut bacteria can trigger immune attacks that damage the brain in patients with ALS and frontotemporal dementia (FTD).
The study, published in Cell Reports, identifies a molecular pathway where harmful microbes in the digestive system produce inflammatory forms of glycogen. These bacterial sugars trigger immune reactions that lead to the death of brain cells.
According to Aaron Burberry, assistant professor in the Department of Pathology at the Case Western Reserve School of Medicine, the findings provide a biological link between gut activity and neurodegeneration. "We found that harmful gut bacteria produce inflammatory forms of glycogen (a type of sugar), and that these bacterial sugars trigger immune responses that damage the brain," Burberry said.
Identifying disease triggers
Testing on 23 ALS and FTD patients revealed that 70% had elevated levels of this harmful glycogen. In contrast, only about one-third of individuals without these diseases showed similar levels.
The discovery may explain why some people carrying the C90RF72 mutation—the most common genetic cause of these diseases—develop symptoms while others do not. The researchers suggest gut bacteria act as an environmental trigger that influences disease progression in genetically at-risk individuals.
Experimental results show that reducing these harmful sugars can improve brain health. Alex Rodriguez-Palacios, assistant professor in the Digestive Health Research Institute, noted that the team was able to reduce these sugars in experiments, which "improved brain health and extended lifespan."
These findings offer new targets for clinical treatments. Scientists are now looking at ways to break down these damaging sugars in the digestive system or develop drugs that disrupt the connection between the gut and the brain.
