Summary: Fecal microbiota transplantation from healthy donors may slow progression in early-stage amyotrophic lateral sclerosis (ALS) by reshaping the gut microbiome and reducing inflammatory responses that contribute to neurodegeneration.
Source: European Society of Clinical Microbiology and Infectious Diseases
A randomized clinical trial is testing whether fecal microbiota transplantation (FMT) from healthy donors can alter immune responses and inflammatory pathways in adults with early-stage amyotrophic lateral sclerosis (ALS), one of the most common motor neuron diseases. The study aims to define relationships between specific gut bacteria and immune cells, especially regulatory T cells (Tregs), which help control inflammation and may influence disease progression.
Preliminary findings from Dr Alessandra Guarnaccia and colleagues at Columbus-Gemelli University Hospital IRCCS in Rome are being presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Copenhagen. Their work explores the gut–immune interactions that could be targeted to slow ALS progression.
ALS causes progressive degeneration of motor neurons in the brain and spinal cord, leading to increasing paralysis, loss of function and, in many cases, death within an average of two to five years. It is the most common form of motor neuron disease, with incidence estimates around 2.8 per 100,000 people in Europe and 1.8 per 100,000 in North America.
About 5–10% of ALS cases are linked to inherited genetic mutations; the remaining 90% are classified as sporadic, with unknown causes. This diversity makes developing a single effective treatment challenging. Current research highlights oxidative stress, excitotoxicity (neuron damage caused by excessive stimulation), and chronic activation of pro-inflammatory pathways as central contributors to neuronal loss in ALS.
Regulatory T cells (Tregs) are key modulators of immune activity. Reduced numbers or impaired function of Tregs has been associated with amplified inflammation around motor neurons. Therefore, strategies that restore or enhance Treg populations are of particular interest as potential neuroprotective therapies in ALS.
Recent research links alterations in the gut microbiome to neurological disorders via the gut–brain axis. Certain bacterial groups, including members of the Proteobacteria phylum, can interact with the immune system and promote pro-inflammatory signaling when Treg control is weakened. Animal studies have found early disruptions in gut microbial communities in ALS models, suggesting the microbiome may play a role in disease onset or progression.
FMT is an established clinical procedure to restore healthy gut microbial balance and modulate local and systemic immunity, most notably used for recurrent Clostridioides difficile infection. The current trial applies this approach in ALS to test whether introducing a healthy donor microbiome can shift immune responses toward a more anti-inflammatory, neuroprotective state.
The randomized study enrolled 42 adults with early-stage ALS (ages 18–70, symptoms present for 18 months or less). Participants were randomly assigned in a 2:1 ratio to receive FMT (28 patients) or to a control group (14 patients). Donor microbiota were infused at baseline and again at six months for those in the intervention arm; control participants did not receive an infusion.
On each treatment day, researchers collected stool, saliva and blood samples to assess changes in gut microbiota composition, immune cell populations, and inflammatory markers. In addition, each participant underwent three endoscopic procedures to obtain intestinal biopsies at baseline, six months and twelve months. These samples are being analyzed to identify early biological processes that might drive ALS progression.
The trial’s primary endpoint is a meaningful increase in circulating Treg numbers in FMT-treated patients compared with controls from baseline to six months. Safety data so far indicate that the FMT procedures have been well tolerated with no reported adverse events.
Early microbiome profiling of six patients at baseline revealed an elevated relative abundance of Proteobacteria—on average about 15%—a group of bacteria with surface components that can readily stimulate immune responses and drive inflammation. This finding supports the hypothesis that a pro-inflammatory gut microbiome may contribute to immune dysregulation in ALS.
“There is a substantial unmet need for ALS therapies, and our study highlights a new pathological pathway we might target,” says Dr Guarnaccia. “If FMT can expand Treg populations and shift immune activity around motor neurons toward an anti-inflammatory, neuroprotective profile, it could slow disease progression.”
Professor Luca Masucci of the Catholic University of the Sacred Heart, Rome, adds: “By mapping how gut bacteria influence inflammatory pathways, we may develop novel therapeutic strategies that interfere with those pathways. We expect to complete analysis of the full trial dataset in 2024.”
ALS affects people across all racial, ethnic and socioeconomic groups. Symptoms typically appear between ages 40 and 70, with an average diagnosis age near 55. Several well-known figures have publicly shared their experience with motor neuron disease, underscoring the wide-ranging impact of ALS. Notably, Professor Stephen Hawking lived for many decades after diagnosis, illustrating the variability of disease course.
About this ALS research news
Author: Simone Brüderli
Source: European Society of Clinical Microbiology and Infectious Diseases
Contact: Simone Brüderli – European Society of Clinical Microbiology and Infectious Diseases
Image: The image is in the public domain
Original Research: Findings presented at ECCMID 2023