new data show.
Nearly three out of four people in a clinical trial experienced fewer symptoms and fatigue and a greater quality of life at both 2 years and 3 years after FMT in Norway. Those FMT-treated patients who relapsed subsequently responded to FMT upon retransplantation, reported the authors, who also correlated individual microbial profiles with clinical outcomes.
The study, led by Magdy El-Salhy, MD, PhD, department of medicine, Stord (Norway) Hospital, was published online in Gastroenterology.
An expert not involved with the study, Brian Lacy, MD, PhD, a gastroenterologist with the Mayo Clinic in Jacksonville, Fla., said that the results of the study are important, but he cautions against treating IBS with FMT outside clinical trials, at least until the protocol is validated, given demonstrated risks.
The new study included 125 patients (104 women, 21 men) in three groups: 38 received a placebo, 42 received 30 g of donor feces, and 45 received 60 g of donor feces. The feces – all from one male donor – was administered to the duodenum.
The response rates for those who received FMT were significantly higher than for those who received placebo. Those receiving 30 g of feces had a response rate of 69.1%, and those in the 60-g group had a response rate of 77.8%, whereas the response rate in the placebo group was 26.3%.
Patients provided a fecal sample and completed five questionnaires at the beginning of the study and at 2 and 3 years after FMT.
Patients in both treatment groups had significantly fewer IBS symptoms – such as abdominal pain, abdominal bloating, dissatisfaction with bowel habits, and quality-of-life interruption – and less fatigue compared with the placebo group, as well as higher quality of life scores at 2 and 3 years.
No long-term adverse effects were reported.
The dysbiosis index decreased only in the treatment group at years 2 and 3.
Microbial modifications correlate with IBS symptoms
In addition, the fluorescent signals of 10 bacteria that had changed after FMT were significantly correlated with improved IBS symptoms and fatigue in both treatment groups.
“Of the bacteria markers whose fluorescence signals changed in the 30-g and 60-g groups, but not in the placebo group, at both 2 and 3 years after FMT, nine were significantly correlated with the total IBS-SSS [IBS–Severity Scoring System] scores,” the authors wrote. One more bacterium with a changed fluorescence signal in the active treatment group also correlated with total fatigue.
Dr. El-Salhy told this news organization that those findings open the door for the select bacteria to be used, for example, in capsule form to treat IBS and fatigue.
The most surprising finding for the team was that the “majority of IBS patients [who] responded to FMT maintained response up to 3 years” or more, said Dr. El-Salhy, alluding to unpublished data up to 5 years.
“Furthermore, 80% of those who relapsed after 3 years responded to a new FMT,” he said.
Women had higher response rates than men at years 2 and 3 after FMT, but there were no differences between complete remission rates of women and men at years 2 and 3.
‘Impressive’ results, but caution warranted
“The results are impressive,” Dr. Lacy said. “I believe that this will help researchers around the world refine their techniques, as we learn more about FMT for the treatment of IBS. It also clearly plays up the importance of the gut microbiome in symptom generation in IBS patients.”
However, he said, until the results are replicated, and the protocol validated, FMT should not be used routinely to treat IBS because there are risks with the procedure.
Dr. Lacy pointed out there have been mixed results in the literature regarding FMT and IBS.
He cited a meta-analysis of four studies (n = 254) in 2019 that did not show a benefit for FMT in patients with IBS. However, a second meta-analysis of five studies (n = 267) did show some benefit, possibly owing to the type of donor and small-bowel infusion.
The authors added that, in the seven randomized, controlled trials investigating FMT for IBS, four concluded that FMT eased symptoms and improved quality of life in patients with IBS, whereas treatment was not effective in the other three.
The authors pointed to differences in protocols, donors, the cohort treated, FMT dose, and route of administration.
The longest response time previously studied in the randomized, controlled trials was 1 year, the authors pointed out. The new study was a 3-year follow-up of these authors’ previous randomly assigned placebo-controlled trial participants.
The ‘super-donor’ concept
The authors of the current study described the single chosen donor as “a healthy male aged 36 years with a normal BMI [body mass index] who was born via vaginal delivery, breastfed, a nonsmoker, was not taking any medication, was treated only a few times with antibiotics, exercised regularly, and consumed a sport-specific diet that was richer in protein, fiber, minerals, and vitamins than the average diet.”
The donor had high microbial diversity, and his fecal bacteria makeup was different from that of 254 healthy subjects for 14 of the 48 bacterial markers investigators tested.
Dr. Lacy said that the “super-donor” concept is noteworthy and an apparent key to success.
“Other studies have not done this,” Dr. Lacy noted.
Among the strengths of the study are that it included a relatively large cohort of patients with IBS, with three IBS subtypes and a single well-defined donor. However, it did not include the fourth IBS subtype, unsubtyped IBS, and it only investigated a part of the intestinal bacterial content, the authors acknowledged.
Most interesting, Dr. Lacy said, is that the IBS subtype did not seem to matter to FMT outcomes at 3 years and that all three subtypes responded better than placebo.
“That’s encouraging,” Dr. Lacy said.
The investigators received a grant from Helse Fonna. The study authors and Dr. Lacy reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.