A groundbreaking discovery by researchers at Case Western Reserve University is offering new hope for understanding and potentially treating two devastating neurodegenerative diseases: Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). The research, published in Cell Reports in February 2026, identifies a surprising link between gut bacteria, the production of specific sugars, and the deterioration of brain cells.
ALS and FTD are both progressive conditions with limited treatment options. FTD primarily impacts personality, behavior, and language, affecting the frontal and temporal lobes of the brain. ALS attacks motor neurons, leading to gradual muscle weakness, and paralysis. While the exact causes of these diseases remain largely unknown – with factors like genetics, environmental exposures, brain injuries, and diet all under investigation – this new study sheds light on a previously unrecognized molecular connection.
The research team, led by Aaron Burberry, assistant professor in the Department of Pathology at Case Western Reserve University School of Medicine, discovered that certain gut bacteria produce inflammatory forms of glycogen, a type of sugar. These bacterial sugars then trigger immune responses that ultimately damage brain cells. “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 explained.
Significantly, the study found that 70% of the 23 ALS/FTD patients examined exhibited dangerous levels of these harmful glycogen compounds, compared to only one-third of individuals without the diseases. This suggests a potential biomarker for identifying individuals who might be at risk or who could benefit from targeted therapies.
This discovery is particularly relevant for individuals carrying the C9ORF72 mutation, the most common genetic cause of both ALS and FTD. The research helps explain why some individuals with this mutation develop the diseases while others do not, pointing to gut bacteria as a key environmental trigger. The study solves a long-standing question about neurodegenerative diseases by identifying this molecular connection.
Beyond identifying the problem, the researchers have also demonstrated a potential solution. Alex Rodriguez-Palacios, assistant professor in the Digestive Health Research Institute at the School of Medicine, and the team were able to reduce the harmful sugars, which “improved brain health and extended lifespan” in preclinical models. This opens the door to exploring treatments that specifically target and break down these inflammatory sugars in the gut.
The unique capabilities of Case Western Reserve University’s Department of Pathology and Digestive Health Research Institute were crucial to this breakthrough. The institute utilizes germ-free mouse models – mice raised in completely sterile environments – allowing researchers to isolate the effects of specific gut bacteria on brain diseases. This is made possible by an innovative “cage-in-cage” sterile housing system developed by Rodriguez-Palacios, a technical capability that few institutions worldwide possess.
Fabio Cominelli, Distinguished University Professor and director of the Digestive Health Research Institute, emphasized the importance of this specialized infrastructure. The system allows for large-scale microbiological studies necessary to understand the complex interplay between the gut and the brain – research that would be impossible with traditional methods.
Looking ahead, Burberry and his team plan to conduct larger studies to understand when and why these harmful microbial glycogens are produced, surveying gut microbiome communities in ALS/FTD patients both before and after disease onset. They also anticipate that clinical trials to assess whether reducing glycogen levels in ALS/FTD patients could slow disease progression could begin within a year.
This research builds on previous work from the same team, published in Science Translational Medicine in February 2024, which identified the role of the C9ORF72 gene and the inflammatory molecule Interleukin 17A (IL-17A) in the development of ALS and FTD. That earlier study showed that blocking IL-17A in mouse models with the C9ORF72 mutation reduced brain inflammation and improved mobility. It identified another gut-derived molecule, CD80, as contributing to inflammation in response to elevated IL-17A levels in the brain. The researchers noted that treatments to block IL-17A are already FDA-approved for autoimmune diseases like psoriasis and rheumatoid arthritis, suggesting a potential pathway for repurposing existing therapies for ALS patients.
The findings represent a significant step forward in understanding the complex relationship between the gut microbiome and neurodegenerative diseases, offering a new avenue for therapeutic intervention and providing hope for individuals and families affected by ALS and FTD.
Reference: McCourt B, Lemr K, Chakrabarti S, et al. C9orf72 in myeloid cells prevents an inflammatory response to microbial glycogen. Cell Rep. 2026;45(2). Doi: 10.1016/j.celrep.2025.116906
