(P034) A RANDOMIZED PLACEBO-CONTROLLED TRIAL OF ALGINATE INTAKE AFTER FECAL MICROBIOTA TRANSPLANTATION FOR ULCERATIVE COLITIS

【Background】

Rectifying imbalances of the gut microbiota with fecal microbiota transplantation (FMT) from healthy donors to patients suffering Ulcerative colitis (UC) have gained clinical interest. Our previous studies suggested FMT following bowel cleansing with amoxicillin, fosfomycin, and metronidazole (Antibiotic FMT: A-FMT) contribute to effective colonization and improved its efficacy. In addition, alginate and its derivatives have been reported to have the potential to induce the growth of intestinal bacteria including Bacteroides members and produce short-chain fatty acids, which are beneficial in regulating overactive autoimmunity. Our trial aims to investigate whether post-intervention with alginate, which can improve the intestinal environment, will enhance the therapeutic effect of A-FMT in UC.

【Methods】

This is a double-blinded, randomized, placebo-controlled, parallel assignment trial. Patients aged 20 years or older suffering from active UC with a Total Mayo Score (TMS) of 3-10 and a Sum Endoscopic Mayo Score of 2 or above participated in this study between September 2020 and September 2022. After rigorous screening, we selected relatives or volunteer donors aged 20 years or older. After 2 weeks of oral administration of three antibacterial agents, 200ml of donor stool suspension was delivered by colonoscopy. After A-FMT, the patients were randomly divided into two groups, and took a bottle of alginate or placebo twice a day for 8 weeks. At 8 weeks after A-FMT, TMS was defined as "response" if TMS was improved ≥ 2 and ≤ 30% of decrease, and "remission" if TMS further improved to ≤ 2. The intestinal microbiota of collected stool was analyzed by 16S rRNA sequencing.

【Results】

53 patients and 19 donors were enrolled in this study and 48 patients completed the study (placebo/alginate group n = 23/25). The response and remission rate were 78.3/43.5% in placebo and 68.0/43.2% in alginate group. There was no significant difference in the change of TMS between in placebo (-3.3 ± 2.3) and alginate group (-3.2 ± 3.2). However, regarding to histological evaluation, alginate group exhibited a significantly higher change compared to placebo group in effective cases (placebo/alginate group n = 18/17, p < 0.04). In microbiota analysis, the relative abundance of Bacteroidota was significantly higher in alginate group than placebo group in effective cases (p = 0.02).

【Conclusion】
Although the therapeutic effect of alginate intake after FMT was not clear in the clinical evaluation, it was suggested that it may contribute to histological remission. Furthermore, the administration of alginate increased relative abundance of Bacteroidota, leading to alterations in the gut microbiota, which may contribute to the therapeutic efficacy of A-FMT.