OBJECTIVES: The aim was to investigate the effect of fecal microbiota transplantation (FMT) on colonic enteroendocrine cells densities in patients with irritable bowel syndrome (IBS). MATERIALS AND METHODS: This study is connected to the REFIT study, a double-blinded placebo-controlled trial to investigate using FMT for IBS treatment. Eighty-three subjects received either donor-FMT or placebo FMT (own feces) by colonoscope to cecum. Biopsies were obtained from sigmoid colon. Ten responders and ten non-responders consented to new biopsy one-year after FMT. Sixteen patients received donor-FMT and four received placebo FMT. Biopsies were immunostained for all of the colonic enteroendocrine cells and were quantified using computerized image analysis.Allocation sequence was revealed after obtaining re-biopsies and cells quantification. RESULTS: Scores for IBS-SSS (mean ± SEM) of responders (eight of 10 patients who received donor FMT) and non-responders changed from baseline to one year after FMT (297 ± 11 and 81 ± 16,  < .0001, and 270 ± 17 and 291 ± 16,  = .15, respectively). Using paired -test to compare enteroendocrine cells densities one-year after FMT to baseline showed significant increase only in somatostatin immunoreactive cells density in the total IBS responders group ( = .023) and who received donor-FMT ( = .038). The densities of peptide YY and enteroglucagon immunoreactive cells increased significantly ( = .04 and .035, respectively) in donor-FMT recipients. No significant changes were noted in placebo FMT or nonresponders subgroups. CONCLUSION: This study shows that colonic enteroendocrine cells densities significantly change in responders group that received donor-FMT. The mechanisms for the cross talks between gut microbiota and colonic enteroendocrine cells remain to be investigated.