Danish researchers have conducted the world's first pilot clinical trials that have shown that faecal transplantation can significantly improve the condition of patients with gastroenteropathy associated with type 1 diabetes. A report on the work has been published in the journal eClinicalMedicine.
Diabetic gastroenteropathy is caused by autonomic neuropathy, dysfunction of Cajal cells, and decreased contractility of intestinal smooth muscle cells in diabetes mellitus. They lead to slow passage of intestinal contents and accumulation of feces, which disrupts the composition of the intestinal microbiota and its interaction with the intestine and central parts of the autonomic nervous system, and increases systemic inflammatory reactions. Manifestations of the disease include nausea, vomiting, abdominal pain, bloating, constipation, diarrhea, and fecal incontinence, which increases morbidity and reduces work capacity and quality of life. The available treatment options are extremely limited.
Stool transplants from healthy people are primarily used to treat pseudomembranous colitis caused by the bacterium Clostridioides difficile, a life-threatening disease that most often develops with long-term antibiotic therapy and is resistant to it. Faecal banks are created for this purpose, and similar drugs have already been approved for clinical use in Australia and the United States. In experiments and trials, it has been successfully used to improve the composition of the gut microbiota after cesarean section and to alleviate symptoms of autism spectrum disorders and Parkinson's disease.
Katrine Lundby Høyer from Aarhus University and colleagues conducted the double-blind, randomised, placebo-controlled phase I FADIGAS trial. They enrolled 20 adult patients with type 1 diabetes for at least five years, severe gastroenteropathy (GSRS-IBS score 40 or more) and no other chronic or infectious gastrointestinal diseases over two years.
Half of them were randomly assigned to receive a single dose of 25 enteric-coated capsules containing a total of 50 grams of feces collected after a thorough examination from eight healthy people, and the other half were assigned a placebo. After four weeks, they were examined and all were openly assigned to receive the feces preparation once, with a second examination after another four weeks. Before and during treatment, they had stool samples taken and their symptoms and quality of life assessed.
After treatment, the median symptom severity according to the GSRS-IBS scale decreased from 58 to 35 points in the main group and from 64 to 56 points in the control group (p = 0.01). The median quality of life associated with gastrointestinal symptoms according to the IBS-IS scale improved from 108 to 140 and from 77 to 92 points, respectively (p = 0.02). Subjective assessment of symptom severity according to the PAGI-SYM scale decreased by a median from 42 to 25 and from 47 to 41 points, respectively (p = 0.03). DNA analysis of the intestinal microbiota of patients demonstrated its significant changes after fecal transplantation towards enrichment and species diversity.
During the trial, 26 moderate and serious adverse events were reported in four patients on active treatment and five on placebo, with no significant difference between groups. None were considered related to treatment. The most common were diarrhea, bloating, and abdominal pain.
Thus, in pilot trials, fecal transplantation was quite safe and reduced the severity of symptoms, improving the quality of life, in patients with gastroenteropathy in type 1 diabetes. More extensive studies will be needed to clarify the data on efficacy and safety, the authors conclude.
Faecal transplantation is generally well tolerated, but isolated side effects and even deaths have been reported throughout its use worldwide.