Early clinical trial testing gut microbe transplants in ALS patients

Research suggests gut microbiome may become dysregulated in some diseases

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A young person raises their shirt to show the torso to another. The gut and the microbiota are visible.

An early clinical trial is testing whether fecal microbiota transplants (FMT) — a procedure that aims to introduce healthy bacteria to the digestive tract — might reduce inflammation among people with amyotrophic lateral sclerosis (ALS).

“With this information, we could potentially provide new approaches for treatments by altering or interfering with these inflammatory pathways,” Luca Masucci, MD, PhD, trial investigator from the Catholic University of the Sacred Heart in Rome, said in a press release. “We hope to have all our data from this trial to [analyze] in 2024.”

The human digestive system is home to billions of bacteria and other microorganisms, collectively known as the gut microbiome. Bacteria in the gut microbiome interact with the body’s own cells to help regulate an array of processes, ranging from controlling immune responses to modulating brain activity.

An emerging body of research has suggested the gut microbiome becomes dysregulated in ALS and numerous other neurological disorders.

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FMT’s goal is to normalize activity of gut microbiome

FMT is a procedure that basically works by collecting bacteria from the digestive tract of a healthy donor, and infusing them into the system of a person with disease. The overall aim is to normalize activity of the gut microbiome.

This clinical trial, FETR-ALS (NCT03766321), is sponsored by Azienda Ospedaliero-Universitaria di Modena and being conducted at several centers in Italy.

The study enrolled 42 people with ALS, who were randomly assigned to receive FMT or a placebo infusion, given at the start of the study and then again six months later. On the day of each procedure, samples of stool, saliva, and blood were collected for analyses.

The main goal of the study is to assess how FMT affects numbers of regulatory T-cells, known as Tregs, a type of anti-inflammatory immune cell that helps slow inflammation. Theoretically, increasing Treg levels may be beneficial in ALS, where abnormal inflammation is thought to play a central role in driving the disease.

Secondary measures include changes in other markers of inflammation and nerve damage, as well as declines in lung function and quality of life, and disease progression.

Preliminary study data, including the initial gut microbiome profiles from six study participants, were recently presented by Guarnaccia at this year’s European Congress of Clinical Microbiology & Infectious Diseases, held last month in Denmark.

Data suggested ALS patients had high levels of bacteria in a group called Proteobacteria, which are thought to have pro-inflammatory effects on immune activity.

“The hope is that FMT will increase the Treg number switching the immune system surrounding motor neurons to an anti-inflammatory, neuroprotective status, and slowing the progression of ALS,” said study investigator Alessandra Guarnaccia of Columbus-Gemelli University Hospital IRCCS. “The unmet need for therapies for ALS is huge, and our work opens up a whole new pathology that we could address.”