A New Understanding of the Gut–Brain Axis

By Dr. Neeharika L. Mathukumalli, Senior Consultant Neurologist and specialist in autoimmune neurological diseases, STAR Hospitals, Banjara Hills

Recent research has strengthened the growing evidence that the gut–brain axis plays a critical role in the development of neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), according to Dr. Neeharika L Mathukumalli, Sr. Consultant in Neurology and specialist in autoimmune neurological diseases at STAR Hospital, Banjara Hills.

Referring to a study published in Cell Reports, Dr. Neeharika explains that certain gut bacteria may produce inflammatory forms of glycogen, a type of sugar, which can trigger immune-mediated damage to brain cells. “This study provides an important biological link between gut microbiota and neuroinflammation, which has been a missing piece in understanding diseases like ALS and FTD,” she said.

How These Diseases Affect the Brain

ALS is a progressive neurological disorder affecting motor neurons, leading to muscle weakness and eventual paralysis, while FTD primarily impacts the frontal and temporal lobes, resulting in behavioral and language disturbances. In most patients, the exact cause of these conditions remains unclear.

Link Between Genetics and Environment

“The findings are particularly relevant because they help explain why some individuals with genetic predisposition, such as C9orf72 mutations, develop these diseases while others do not,” Dr. Neeharika noted. “It suggests that environmental factors, especially gut microbiome alterations, may influence disease onset and progression.”

According to the study, nearly 70% of patients with ALS and FTD were found to have elevated levels of harmful bacterial sugars, compared to about one-third of individuals without these conditions. “This difference is clinically significant and points toward a potential modifiable pathway,” she added.

Rising Disease Burden

Globally, ALS affects approximately 2–3 individuals per 100,000 population, and FTD accounts for around 10–20% of early-onset dementia cases. Notably, nearly 90% of ALS cases are sporadic, without a clear inherited cause, further highlighting the importance of identifying non-genetic contributors.

Why the Gut Matters

Dr. Neeharika emphasized that the human gut microbiome plays a major role in regulating the immune system. “The gastrointestinal system hosts trillions of microorganisms and is closely linked to immune function. Any imbalance in this system can have far-reaching effects, including on brain health,” she explained.

Implications for Future Treatment

From a treatment perspective, the findings open up new possibilities. “Targeting the gut microbiome—either by reducing harmful bacterial metabolites or modifying microbial composition—could emerge as a future therapeutic strategy,” she said. Early experimental data suggest that reducing these harmful sugars may improve neurological outcomes.

However, she cautioned that more clinical trials are needed before such approaches become part of routine care. “While the findings are promising, they should be seen as an early step toward understanding disease mechanisms rather than an immediate solution,” she noted.

Importance of Early Awareness

Dr. Neeharika also highlighted the importance of early awareness. “Neurodegenerative diseases often have a long preclinical phase. Identifying early biological triggers, such as gut-related inflammatory signals, may help in early diagnosis and intervention,” she said.

She added that maintaining gut health through balanced nutrition and lifestyle measures may play a supportive role, although its direct impact on preventing these diseases remains uncertain.

A Shift in Neurology

“This research represents a shift in how we approach neurological disorders,” Dr. Neeharika concluded. “It reinforces the idea that brain health is interconnected with the gut, and future treatments may need to address this broader interaction.”