Randomised Clinical Trial

Faecal Microbiota Transplantation Versus Autologous Placebo Administered Via Colonoscopy in Irritable Bowel Syndrome

Perttu Lahtinen; Jonna Jalanka; Anna Hartikainen; Eero Mattila; Markku Hillilä; Jari Punkkinen; Jari Koskenpato; Veli-Jukka Anttila; Jyrki Tillonen; Reetta Satokari; Perttu Arkkila


Aliment Pharmacol Ther. 2020;51(12):1321-1331. 

In This Article

Abstract and Introduction


Background: Irritable bowel syndrome (IBS) has been associated with microbial dysbiosis.

Aim: To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of IBS.

Methods: Forty-nine IBS patients were randomised to receive autologous or allogenic FMT via colonoscopy. The primary endpoint was a sustained, minimum of 50-point, reduction in the IBS Symptom Severity Score. The secondary outcomes were levels of anxiety and depression, changes in quality of life, gut microbiota and faecal water content as assessed with validated questionnaires, intestinal microbiota composition and stool dry weight.

Results: The primary endpoint was not achieved in either group. However, there was a transient reduction in the mean IBS Symptom Severity Score in the FMT group at 12 weeks after treatment as compared to baseline (P = 0.01). The groups did not differ in the number of patients achieving clinical response at 12 weeks. In the FMT-treated patients, microbial composition had changed to resemble that of the donor and the stool water content decreased significantly compared to baseline. The depression score decreased in patients with a reduction in IBS symptoms after FMT, but not in those placebo-treated patients who experienced a reduction in IBS symptoms.

Conclusions: FMT provided only a transient relief of symptoms, although it induced a sustained alteration in the microbiota of IBS patients. Therefore, FMT delivered by a single infusion via colonoscopy cannot be recommended as a treatment for IBS in clinical practice.


Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. The global prevalence of IBS is approximately 10%, although estimates vary greatly depending on the studied population and which diagnostic criteria are used.[1,2] The widely applied diagnostic criteria Rome III-IV divide the patient phenotypes according to their most dominant bowel characteristics into diarrhoea predominant, constipation predominant, mixed and unsubtyped IBS.

The aetiology of IBS remains unknown although many theories have been proposed. Altered gut motility, epithelial hyperpermeability, low-grade inflammation, visceral hypersensitivity, epigenetics and genetics, altered gut-brain interaction and psychological stressors have all been reported in patients with IBS.[1] In some IBS-patients, psychological factors play a role in the severity and persistence of symptoms; these may also affect the decision to seek health care and alter the response to the provided treatment.[3] IBS has been particularly associated with anxiety and depression, for example IBS-patients have a three-fold risk of suffering from either depression or anxiety in comparison to the general population.[4]

The expanding understanding of the microbiota's multiple functions for human health and its ways of interacting with the host highlight the possible role played by gut microorganisms in the pathogenesis of IBS.[5] It is known that the incidence of IBS is markedly increased after infectious gastroenteritis.[6,7] Furthermore, several studies have detected alterations in the gut microbiota composition between IBS patients and healthy controls, however, a microbiota typical for IBS patients has not been conclusively defined.[5,8,9] Further evidence of the microbial component in IBS is provided by the fact that consumption of microbiota modifying agents such as antibiotics[10] and probiotics[11] has been shown to be effective in reducing IBS symptoms. Regardless of the suspected causal relation between IBS and the intestinal microbiota, it is difficult to obtain convincing supportive evidence due to the multifactorial aetiology of the disorder, the significant heterogeneity in patients as well as the complexity of the gut microbiota. We postulated that the role of the microbiota in IBS could be clarified by altering the composition of the intestinal microbiota in IBS patients by transplanting them with a complex microbial population, that is faecal microbiota transplantation (FMT).

FMT has been shown to be highly effective in treating recurrent Clostridioides difficile infections (rCDI). Although comparative trials between different administration routes are lacking, in this patient group, colonoscopy is often considered as the optimal route.[12] The excellent treatment efficacy in rCDI-patients and its favourable safety profile have encouraged investigators to seek other avenues for FMT research.[13] Data from rCDI-patients indicate that FMT may also relieve functional GI-symptoms as our recent results revealed that rCDI-patients treated with FMT experienced less severe GI-tract symptoms over the long-term than rCDI-patients treated with antibiotics only.[14] Furthermore, FMT for rCDI alters the microbiota of the recipient to resemble that of the donor, a change lasting for at least 12 months.[15,16] Currently, the long-term engraftment of the transplanted microbiota has not been as well documented in patient groups other than rCDI.

There are five recent placebo-controlled trials investigating FMT in IBS with conflicting results.[17–21] In two of these trials, a single faecal transplantation was administered via coloscopy,[17,19] in two of the studies, faecal capsules were given for 3–12 days[18,20] and yet in another trial, FMT was administered via gastroscopy.[21] In summary, FMT via colonoscopy resulted in a modest, but transient, decrease in IBS symptoms,[17,19] the FMT capsules did not exert any benefits[18,20] but FMT via gastroscopy achieved a clear benefit with an up to 89.1% response rate.[21] Although all these three administration routes, that is capsules taken orally for 12 days or a single FMT via colonoscopy or gastroscopy, altered the microbiota of IBS patients towards that of the donor,[18] a concurrent decrease in the symptoms was observed only when FMT was administered via colonoscopy[19] or gastroscopy.[21] Given the mixed results, the efficacy of FMT in IBS seems to depend not only on the microbiota of the donor, but perhaps also on some other element of the stool, or on the survival of key elements of the microbiota while the stool is processed.

It remains unclear whether FMT can sustainably alter the microbiota of IBS patients and how the microbial changes relate to IBS symptoms. Thus, the aim of this study was to evaluate the long-term efficacy of FMT administered via colonoscopy in reducing IBS symptoms in a randomised, double-blinded and placebo-controlled clinical trial, where the patients were monitored for one year. We also studied the impact of FMT on the quality of life, depression and anxiety of IBS patients. Furthermore, we measured the long-term changes in microbiota and stool consistency after a single FMT.