Gut microbiome and neurodegeneration: a new therapeutic lever

By Elodie Vaz  | Published on February 12, 2026 | 3 min read

  Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) rank among the most severe and least understood neurodegenerative diseases. FTD preferentially affects the frontal and temporal lobes, causing major changes in behavior, personality, and language. ALS is characterized by progressive degeneration of motor neurons, leading to irreversible muscle weakness that advances to paralysis.

Despite the identification of genetic mutations—most notably C9ORF72 (often misspelled as “C90RF72”)—the origin of these conditions remains largely unknown, suggesting that environmental factors may modulate their clinical expression.

Understanding clinical variability among mutation carriers

A team at Case Western Reserve University sought to address a fundamental question in a study published in February 2026 in Cell Reports: why do some carriers of ALS/FTD-associated mutations develop disease while others remain asymptomatic? Their hypothesis was based on a functional link between the gut microbiome and brain degeneration, mediated by immuno-inflammatory mechanisms involving the gut–brain axis.

Glycogen as an immuno-neurotoxic trigger

To reach their conclusions, the researchers analyzed the gut microbiome of 23 ALS/FTD patients to quantify bacterial glycogen production. “We discovered that harmful gut bacteria produce inflammatory forms of glycogen and that these bacterial sugars trigger immune responses that damage the brain,” said Prof. Aaron Burberry, the study’s lead investigator and assistant professor in the Department of Pathology at the Case Western Reserve University School of Medicine, in a press release. He reported that 70% of the 23 ALS/FTD patients had dangerous glycogen levels, compared with only one-third of unaffected individuals.

An emerging biomarker and therapeutic target

In parallel, the team used germ-free mouse models raised in fully sterile environments, enabled by a “cage-in-a-cage” system developed by Alex Rodriguez-Palacios, assistant professor at the Digestive Health Research Institute of the School of Medicine and co-author of the study. This technology allows the selective introduction of specific gut bacteria and the observation of their direct effects on the brain.  

Prof. Rodriguez-Palacios stated that the team then leveraged these findings to reduce harmful sugars, which “improved brain health and extended lifespan.”

Toward microbiome-targeted clinical trials

  These results establish a direct molecular link between the gut microbiome and neurodegeneration. They help explain why some individuals carrying the C9ORF72 mutation develop ALS or FTD while others do not, by identifying gut bacteria as a key environmental triggering factor. The study also highlights bacterial glycogen as a potential biomarker and an innovative therapeutic target.  

This advance places the gut–brain axis back at the center of ALS and FTD pathophysiology. “To understand when and why harmful microbial glycogen is produced, the team will soon conduct larger-scale studies of the gut microbiome in ALS/FTD patients before and after disease onset,” Prof. Burberry explained.  

He added: “Our findings also support clinical trials to determine whether breaking down glycogen in these patients could slow disease progression—trials that could begin within a year.”  

This discovery therefore opens a new therapeutic era in which targeting the microbiome could become a central strategy against neurodegenerative diseases. It paves the way for the testing of new treatments that degrade harmful sugars in the gut and for the development of drugs acting on the gut–brain connection, potentially offering renewed hope for patients affected by these devastating brain disorders.  





About the author – Elodie Vaz 
Health journalist, graduated from the CFPJ in 2023, Élodie explores the marks that illnesses leave on bodies and, more broadly, on human life. A state-registered nurse since 2010, she spent twelve years at patients’ bedsides before trading her stethoscope for a notebook. She now examines the connections between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.