Discussion
enema, CF
ADVERSE EVENTS
To our knowledge, this is the first trial to evaluate how fluid similar to FMT is distributed in the colon immediately after delivery by colonoscopy or enema. CF delivered to the cecum by colonoscopy is indeed distributed across colon, which we saw in all participants. Following CF by enema, most patients had CF distributed to the transverse colon, and some even to the cecum, which contradicts the assumption that FMT delivered as enema is only distributed to the distal colon (i.e. rectum and sigmoid colon) [It is reasonable to believe that better FMT distribution increases the chance of donor microbiota engraftment, which has been shown to be associated with treatment outcome [Treatment cost, procedure invasiveness and risk of adverse events should be considered when choosing administration method. FMT by enema have the advantage that it can be given bedside, requires little training of the healthcare personnel performing the procedure and involves fewer adverse events than colonoscopy [The distribution of FMT delivered by enema may vary because of individual differences in colon anatomy. Studies have shown that the transverse colon is the major determinant of colonic length and that longer transverse colon is more tortuous with sharp-angles [Strengths of our trial is the use of a fluid proven to have the same viscosity as FMT, direct comparison of different methods in the same individual (i.e. same anatomy), standardized procedure for administration methods and outcome assessor blinding (X-ray evaluation).The main limitationAnother limitation is that the enema probe was visualized on the abdominal x-rays in a few patients, which could compromise blinding (i.e. probe was only inserted at enema). As the outcome assessors were not familiar with the enema procedures it is unlikely that this interfered with the blinding. Further, the enema + procedure used in our trial deviates slightly from how we recommend performing the procedure outside the trial: To obtain an abdominal X-ray from both enema ÷ and enema + procedures from one enema delivery, patients were lifted in a supine position after CF delivery by enema and returned to a supine position after the first X-ray (Fig. 