Fecal microbiota transplantation may change gut microbiota composition but placebo improves symptoms in IBS patients

Previous research has shown that some subgroups of patients with irritable bowel syndrome (IBS) exhibit a different gut microbiota composition. Although previous small not blinded studies and one randomized placebo-controlled study have looked at the effectiveness of fecal microbiota transplantation (FMT) in patients with IBS, its utility in these patients remains unknown.

A new randomized, double-blind placebo-controlled study, led by Dr. Andreas Munk Petersen from the Department of Gastroenterology at Copenhagen University Hospital Hvidovre (Denmark), has shown that FMT capsules may change the gut microbiota of patients with IBS without relieving their symptoms. In fact, patients receiving placebo capsules did significantly better than after FMT.

In order to test the effects of FMT on gut microbiota composition and symptoms in patients with IBS, 52 adult patients with moderate-to-severe IBS (all IBS subtypes) were randomized to FMT or placebo capsules using donor-mix FMT for 12 days and then monitored for six months. Patients in the two groups were comparable and at the moment of inclusion there were 25 patients in the intervention group and 26 in the placebo group.

Fecal samples were collected at baseline, three days after FMT treatment had stopped and prior to each visit at 1, 3 and 6 months. Furthermore, both IBS disease severity and alterations in quality of life were registered using the IBS-severity scoring system and IBS-specific quality of life, respectively.

Although an overall reduction of IBS symptoms was observed within each group between inclusion and during follow-up, in comparison with the FMT group, the placebo group was the only one to experience a significant improvement in the IBS-severity scoring system between inclusion and both 3 and 6 months. Significant effects were only seen among patients with IBS-related constipation in the placebo group. Similarly, the improvements in IBS-specific quality of life were significantly better in the placebo group 1, 3 and 6 months after inclusion.

Regarding the change in gut microbiota composition before and after treatments in patients with IBS, at baseline (both intervention and placebo groups), said patients showed lower levels of gut microbiome a-diversity when compared with healthy fecal donors. Furthermore, patients receiving FMT capsules showed an increase in a-diversity, making this group indistinguishable from the donors, while placebos did not have the same effect.

Gut microbiome b-diversity analysis showed that taking FMT capsules meant the FMT group’s gut microbiota resembled the donors’ gut microbiota. Interestingly, a specific tracking software showed that the FMT capsules resulted in the establishing of donor microbes in the recipients at 6 months, with 11 operational taxonomic units established in the FMT treatment group that were not established in the placebo group. Changes in the gut microbiota composition were not affected by IBS subgroups. These findings support the lasting impact of FMT capsules on the recipients’ gut microbiota, while the changes in gut microbiota composition did not correlate with clinical outcomes.

No serious adverse events were reported among patients during the 6-month follow-up; however, 6 patients with FMT and none with placebo reported diarrhea as adverse event during the study. This and the overall symptom improvement following placebo but not with FMT leaves an important question: Is FMT doing harm rather than benefitting patients with IBS. While the study cannot answer this, it allows a speculation how this paradoxical response might have occurred: All patients received a thorough bowel cleansing prior to the intervention, and this may be responsible for the clinical response in the placebo group, while FMT may have abolished this beneficial effect, despite its action on the microbiota.

In conclusion, this is the first study that has simultaneously studied the impact of FMT on IBS symptoms and changes in the gut microbiota’s composition. Although FMT capsules may increase gut microbiome diversity regardless of IBS subgroups, no impact on symptom relief was identified, but maybe symptom worsening in a few cases.

 

 

Reference:

Halkjær SI, Christensen AH, Lo BZS, et al. Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study. Gut Epub ahead of print: 7 August 2018. doi: 10.1136/gutjnl-2018-316434.

Enck P. Primum non nocere: is fecal microbiota transplantation doing harm to IBS patients? Gut. 2018. doi: 10.1136/gutjnl-2018-317277.

Paul Enck
Paul Enck
Prof. Dr. Paul Enck, Director of Research, Dept. of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Germany. His main interests are gut functions in health and disease, including functional and inflammatory bowel disorders, the role of the gut microbiota, regulation of eating and food intake and its disorders, of nausea, vomiting and motion sickness, and the psychophysiology and neurobiology of the placebo response, with specific emphasis on age and gender contributions. He has published more than 170 original data paper in scientific, peer-reviewed journals, and more than 250 book chapters and review articles. He is board member/treasurer of the European Society of Neurogastroenterology and Motility and of the German Society of Neurogastroenterology and Motility, and has served as reviewer for many international journals and grant agencies.