The Optimal Route of Fecal Microbiota Transplantation for Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common functional disorder affecting approximately 10% globally.\[1\] It is often referred to as benign, although, when severe, may cause significant reduction of quality of life and work absenteeism. The etiology of IBS is 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. 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. Fecal microbiota transplantation has over 90% efficace in recurrent Clostridioides difficile infection (rCDI), for which it has been in clinical use for a decade. FMT is currently recommended after the second relapse of rCDI. FMT is recommended to be considered only in clinical trial settings for other indications than rCDI. Randomized controlled studies in FMT for IBS have conflicting results. In studies with a single administration of FMT in colonoscopy a mild transient reduction of IBS symptoms has followed the intervention. In studies with fecal capsules there has not been any benefit observed. FMT via gastroscopy exerted a clear benefit with an up to 89.1% response rate. These surprisingly good results were thought to be contributable to careful donor selection, however the study included only one donor and no specific characteristics of microbiota were indentified of the suspected superdonor. Although all these three administration routes altered the microbiota of IBS patients towards that of the donor, a concurrent decrease in the symptoms was observed only when FMT was administered via colonoscopy or gastroscopy. Manipulation of microbiota through FMT remains to be potential treatment option for IBS, however, several mechanistic questions await answering. Investigators do not yet know what is the component of stool which would carry the healing potential. There needs to be further research to define optimal donors as well as optimal patients who would be prone to benefit of FMT. The amount and number of FMT treatments may be a factor contributing to the outcome. It is also undefined in which extend does the route of administration of FMT contribute to the outcome in IBS patients. Therefore, the investigators present a placebo-controlled trial "the optimal route" to provide further mechanistic knowledge of the optimal FMT protocol in this patient group.