BACKGROUND: To investigate the effects of colonoscopic administration of probiotics on patients with irritable bowel syndrome with predominant diarrhea (IBS-D) by a single-center, randomized-controlled trial. METHODS: Consecutive outpatients at the First Affiliated Hospital of Fujian Medical University who met the Rome IV diagnostic criteria for IBS-D (n = 22) and healthy subjects (n = 10) from January 2017 to January 2018 were enrolled. IBS-D patients were randomly divided into either the probiotics or the placebo group. During the colonoscopy examination, a suspension of live combined Bifidobacterium with Lactobacillus tablets and normal saline was sprayed into the right colon of patients in the probiotics and the placebo group, respectively. All subjects' clinical data and stool samples were collected before, 2 weeks and 4 weeks after colonoscopic treatment. RESULTS: Twenty-nine subjects completed the follow-up. A significant difference was found in the frequency of defecation at 2 weeks, and the abdominal Visual Analog Score and Bristol stool scale at 4 weeks after probiotics treatment. The gastrointestinal symptom rating scale and IBS severity score decreased significantly and the IBS Quality of Life Instrument score increased 2 weeks after probiotics treatment (p <
0.05). The comprehensive therapeutic index was 70.0% and 44.4% in the probiotics group and the placebo group, respectively. The gut microbiota diversity was not significantly different at 2 and 4 weeks after treatment among the groups. Ratio of Firmicutes to Bacteroidetes decreased in the probiotics group. CONCLUSIONS: The symptoms of IBS-D could be improved by probiotics administration via colonoscopy. The study was registered on chictr.org.cn (ChiCTR-IPR-17010411).