FMT Shows Promise for Type 1 Diabetes, Gastroenteropathy Treatment in Pilot Trial

Katrine Lundby Høyer, MD

Credit: Steno Diabetes Center Aarhus

Fecal microbiota transplantation (FMT) may offer a safe and effective treatment option for patients with type 1 diabetes and gastroenteropathy, according to findings from a recent study.¹

The clinical pilot trial, coined “Faecal microbiota transplantation for patients with diabetes type 1 and severe gastrointestinal neuropathy” (FADIGAS), represents the first randomized trial of FMT in patients with type 1 diabetes and symptoms of severe diabetic gastroenteropathy. Results showed FMT was safe, reduced gastrointestinal symptoms, and improved quality of life.¹

“The patients experienced a significant improvement in their quality of life and symptoms, far beyond what we observed with placebo,” lead investigator Katrine Lundby Høyer, MD, of the department of hepatology and gastroenterology at Aarhus University Hospital, said in a press release.² “This is the first time FMT has been tested specifically in this patient group with placebo as a control. The results are very promising.”

The randomized, double-blinded, placebo-controlled trial was conducted between June 2021 and May 2023 at Aarhus University Hospital. It enrolled 20 adult patients who had been diagnosed with type 1 diabetes for > 5 years and had a Gastrointestinal Symptom Rating Scale–Irritable Bowel Syndrome (GSRS-IBS) questionnaire score ≥ 40.¹

Investigators randomly assigned participants in a 1:1 ratio to receive either encapsulated FMT (n = 10) or placebo (n = 10). Patients, investigators, and study personnel with patient contact were blinded to the assigned treatment. Of note, all patients eventually received FMT as a second intervention.¹

Before each treatment, patients were required to fast for ≥ 6 hours for solid food and 2 hours for liquids and were instructed to take 10 mg oral metoclopramide 10 min before ingesting the capsules.¹

​​Participation in the trial lasted for 3 months and comprised 8 outpatient visits. The study’s primary endpoint was the number of adverse events ≥ severity grade 2 as assessed by the Common Terminology Criteria for Adverse Events during the week following the first intervention. Secondary endpoints included gastrointestinal symptoms and quality of life assessed 4 weeks after treatment.¹

The study population was predominantly female (70%) with a median age of 46 (interquartile range [IQR], 32–52) years and a median type 1 diabetes duration of 31 (IQR, 19–36) years. Investigators noted the patients had a high degree of neuropathy and many gastrointestinal symptoms, evidenced by a median baseline COMPASS-31 score of 49 (IQR, 30–55) and a median GSRS-IBS score of 59 (IQR 54–69) at the time of inclusion.¹

During the first intervention, 26 adverse events ≥ grade 2 occurred, including 4 patients in the FMT group who reported 7 adverse events and 5 patients in the placebo group who reported 19 adverse events, with no differences between the groups. The most frequent adverse events were diarrhea, bloating, and abdominal pain. Investigators noted no serious adverse events were related to the treatment.¹

Patients who received FMT reduced their median GSRS-IBS score from 58 (IQR, 54–65) to 35 (IQR, 32–48), whereas patients who received placebo reduced their score from 64 (IQR, 55–70) to 56 (IQR, 50–77; P = .01). Investigators also pointed out the Irritable Bowel Syndrome Impact Scale score improved from 108 (IQR, 101–123) to 140 (IQR, 124–161) with FMT and 77 (IQR, 53–129) to 92 (IQR, 54–142) with placebo (P = .02), while the Patient Assessment of Gastrointestinal Symptom Severity Index declined from a median of 42 (IQR, 28–47) to 25 (IQR, 14–31) after FMT and 47 (IQR, 31–69) to 41 (IQR, 36–64) after placebo (P = .03).¹

To assess if the microbiome of patients receiving FMT changed from before treatment to 4 weeks after, investigators compared the alpha diversity (richness) and beta diversity (Aitchison) between the baseline and the first intervention for each patient. They noted FMT treatment changed the patient microbiome diversity more than placebo.¹

Investigators outlined multiple limitations to these findings, including the fact that it was a pilot study with a small number of participants and limited follow-up; uncertainties regarding the benefit of FMT in patients with less severe symptoms; the use of questionnaires developed for patients with irritable bowel syndrome due to a lack of validated questionnaires for gastroenteropathy in patients with type 1 diabetes; and the risk of interdependence in patient outcomes due to the use of 8 donors for 20 trial participants.¹

“We now need to investigate how the treatment can be implemented more broadly and ensure it becomes accessible to patients with the greatest need,” said Klaus Krogh, MD, PhD, professor and chief physician in the department of hepatology and gastroenterology at Aarhus University Hospital.² “Many have collaborated on this study, and the results look like a breakthrough. I hope we will have the opportunity to conduct further research in the coming years.”

References

1. ^{Lundby Høyer K, Dahl Baunwall SM, Smed Kornum D, et al. Faecal microbiota transplantation for patients with diabetes type 1 and severe gastrointestinal neuropathy (FADIGAS): a randomised, double-blinded, placebo-controlled trial. eClinicalMedicine. doi:10.1016/j.eclinm.2024.103000}
2. ^{Aarhus University. Fecal transplantation offers new hope for diabetes patients with severe gastrointestinal issues. EurekAlert! January 8, 2025. Accessed January 9, 2025. https://www.eurekalert.org/news-releases/1069871}