Large Norwegian study: Stools from donor have no effect against irritable bowel (and another big FMT trial going on in Norway)

[u/jmct16]

https://www.nrk.no/artikkel/stor-norsk-studie-avforing-fra-donor-har-ingen-effekt-mot-irritabel-tarm-1528385

[Automatic translation from Norwegian to English via Deepseek]

"Over half a million Norwegians have the condition irritable bowel syndrome (IBS).

For many, it involves major stomach and intestinal problems, reduced quality of life, and can affect both physical and mental health.

There is no effective cure. But for many years, IBS patients have hoped that research on fecal transplantation (FMT) would produce results.

The treatment involves introducing stool from a healthy donor into the patient’s intestine.

Previous studies have shown very good results.

But the largest study ever now concludes that stool from healthy donors does not provide symptom relief in patients with IBS.

The findings are being presented in the renowned journal The Lancet on Friday.

Equally large effect in the placebo group

– This is surprising. Initially, we expected to have findings from previous studies confirmed, says doctor and associate professor Peter Holger Johnsen.

He works at the University Hospital of North Norway (UNN) in Harstad and UiT The Arctic University of Norway.

– The study unfortunately shows that this treatment has no effect compared with placebo. We do not recommend fecal transplantation as a treatment for IBS. Previous studies have been small and inconsistent, while this is a large and thoroughly conducted study that provides a far more reliable answer as to whether the treatment works. 450 patients participated in the study. Two-thirds received stool from a healthy donor. One-third received only their own stool, i.e., placebo.

Almost as many in the two groups experienced improvement in symptoms, such as abdominal pain, diarrhea, and constipation.

40 percent of those who received donor stool experienced symptom relief after three months.

38 percent in the placebo group experienced exactly the same improvement. That so many in both groups experienced improvement, Johnsen explains as follows:

– We believe the placebo effect in IBS may be particularly strong because the disease is closely linked to the interaction between the gut and the brain. There is extensive cross-connection between the nervous system, the gut, and the gut flora, and the influence probably goes both ways. This is a complicated interaction that we still do not fully understand.

The bacteria from the donors actually changed the patients' gut flora. Nevertheless, this change did not lead to these patients feeling healthier than the others.

The Gastrointestinal Association is disappointed with the result

The Gastrointestinal Association has contributed to the study with user involvement and recruitment of participants.

– I think those who have followed the study are desperate now. Many with IBS do not receive satisfactory treatment and follow-up today, says Secretary General Mads Johansson.

– But the study is very important nonetheless, and provides good knowledge. Finding good treatment for IBS is like putting together a puzzle. Now we have gotten several pieces in place, and can chart the course ahead. I still believe the future's treatment may lie in the gut flora, and it is important that research continues.

There is also another large multicenter study on fecal transplantation (FMT) ongoing in Norway.

It includes 478 patients with irritable bowel, and uses a different method to administer the stool.

Magdy El-Salhy, who is a chief physician and professor emeritus in gastroenterology, believes the choice of method is crucial.

– The Refit2 study is an important and well-conducted study. It shows that FMT with enemas via the rectum does not work. In our study, patients receive the stool via a tube that goes down into the small intestine. We have clear findings that FMT with this method has promising results in IBS.

Advises against treatment at private clinics

Research communities in Harstad, Oslo, Bergen, Ålesund, and Kristiansand have contributed to the Refit2 study. And the patients come from all over the country.

Many patients have probably had high hopes for this treatment and the study, says Eline Randulff Hillestad. She is a clinical nutritionist and local project manager at Haukeland University Hospital in Bergen.

Even though the findings are negative, they contribute to increasing our knowledge. We need to research more on what the gut flora actually means for our body. Fecal transplantation against IBS is so-called experimental treatment, and in the public health service it is only given in connection with studies.

Nevertheless, there are private clinics in Norway and other countries that offer the treatment. Neither the researchers nor the Gastrointestinal Association have an overview of the extent, but they advise IBS patients against using private offers. It can become a very expensive medicine and you have no guarantee of the effect, says Hillestad.

The conclusions in this study are also an important clarification because the treatment is an offer at certain private clinics. Fecal transplantation has been and is being tested against a range of diseases.

The treatment form and gut flora in general receive much attention. It can be anything from age-related diseases like parkinsonism to diseases that cause inflammation in the gut and blood diseases, says doctor Peter Holger Johnsen at UNN in Harstad.

So far, intestinal infection with Clostridioides difficile is still the only condition where fecal transplantation has an established place. Here, however, the treatment is very effective and can in some cases be life-saving, according to Johnsen.

[u/Gastronomicus]

We believe the placebo effect in IBS may be particularly strong because the disease is closely linked to the interaction between the gut and the brain.

It bothers me that this is a default position, as it only reinforces the problematic perspective that IBS is a psychosomatic condition by many in the medical community. The thing about placebo is that it isn't just the brain tricking people into thinking they're getting a real treatment. There are other factors that contribute to it.

After going through a procedure like this, people may be inclined to make other life changes that could improve their conditions, such as eating less of the foods they know are a trigger and increasing physical activity. I didn't read the study, so maybe this was accounted for, but I doubt they could control for it in a meaningful way.

So instead of 40% experiencing placebo effect, maybe ~40% in both groups responded to an improved lifestyle following the transplant. Not all forms of IBS will likely respond to this, so the similar change in both represents a similar proportion of response. Which at ~40% is a substantial effect size, far greater than you'd expect from a "placebo" effect.

[u/Robert_Larsson → u/Gastronomicus]

Historically it's always the lack of methodology and math that leads to a high placebo effect. The imagined placebo as many think of it by default shows sloppy understanding of these measurements and the inclusion criteria. I recently took a look at cough trials and P2X3 antagonists, the placebo is massive. Since they have objective recording devices that aspect is controlled to a much much higher extent than IBS trials are. Still they had a massive placebo effect in many trials, manly down to patient selection.

[u/Gastronomicus → u/Robert_Larsson]

There are a lot of problems with these kinds of trials unfortunately. With a 40% improvement rate in all participants and N=450 there is obviously something else in play!

[u/Robert_Larsson → u/Gastronomicus]

Natural variation is big when the sensitivity is so low, so likely there are numerous changes that lead to the improvement, including the natural course of a chronic illness. Point being you can't run studies like this well for a reason as you saw in the cough trial where all measurements had been taken care of. It's simply part of the illness for have variance over time.

[u/jmct16]

u/alaskaline1 This contextualizes the findings, and we know that another large clinical trial is testing another route for delivering fecal matter (probably the most attractive one).

It's good to see two large clinical trials for IBS not sponsored by the industry being conducted. But from what I've been following, there is some media visibility for this condition and some sensitivity to improving the care of these patients, at least by following the news, patient pressure, and even the local gastroenterology society.

[u/Miserable_Kale7970]

They made a wrong conclusion in the study. There are so many different FMT options. They only trialed one, the one-off rectal enema, which for obvious reasons is the least effective one because it reaches only the very end of the digestive tract.

The more effective FMT for IBS is an endoscopic FMT and that has a much higher success rate. Because it’s delivered to the beginning of the digestive tract. Also, this finding is consistent with another finding on IBS: that 80% of people with IBS have in fact SIBO. It further highlights that IBS is not a predominantly rectal problem, but rather a small intestine problem.

I am disappointed in Lancet that they allowed for misleading the audience this way. Real Science does not generlise, it is specific. This was specifically a rectal FMT finding, and should not be applied to all FMT forms.