Abstract Background We previously demonstrated the efficacy of antibiotic fecal microbiota transplantation (A-FMT) in patients with UC. To further improve therapeutic outcomes, we examined whether post-A-FMT administration of alginate, a marine-derived polysaccharide, could enhance efficacy and investigated its mechanisms in experimental colitis models. Methods A randomized, double-blind, placebo-controlled trial was conducted in active UC patients (Total Mayo Score TMS 3–10; a Sum Endoscopic Mayo Score ≥2) aged ≥20 years between September 2020 and September 2022. After a 2-week antibiotic regimen (amoxicillin, fosfomycin, and metronidazole; AFM), 200 ml of donor stool suspension was delivered by colonoscopy. From the next day, participants received an alginate (4 g sodium alginate per 150 g bottle) or placebo twice daily for 8 weeks. At 8 weeks after A-FMT, clinical response was defined as ≥ 2-point and ≥30% TMS reduction, and remission as TMS ≤2. Gut microbiota was analyzed using 16S rRNA sequencing. To explore mechanisms, dextran sulfate sodium (DSS)-induced colitis mice were used. Microbiota composition was evaluated by 16S rRNA sequencing, and metabolomic (CE-TOFMS) and transcriptomic (RNA-seq) analyses were performed to identify alginate-responsive metabolites and host genes. The epithelial repair effect was further assessed in gene-deficient mice and colon organoid cultures. Results A total of 53 patients and 19 donors were enrolled, and 48 patients completed the trial (placebo/alginate = 23/25). Response and remission rates were 78.3% and 43.5% in the placebo group, and 68.0% and 43.2% in the alginate group, respectively. Although clinical remission did not differ significantly, the alginate group showed greater histological improvement (p 0.04). Among alginate responders, the relative abundance of Bacteroidota increased significantly (p = 0.02), and fecal taurine levels positively correlated with Bacteroidota abundance. Alginate significantly suppressed body weight loss and mucosal damage in DSS-induced colitis mice and increased Bacteroides and Lactobacillus. These bacteria exhibited bile salt hydrolase activity, liberating taurine from conjugated bile acids and elevating intestinal taurine levels. Both alginate and taurine upregulated expression of a specific gene in the intestinal epithelium, while the gene deficiency impaired epithelial regeneration in mice and colon organoids. Conclusion Alginate regulates taurine metabolism through gut microbiota alterations and promotes mucosal healing by activating the specific gene in colonic epithelial tissue. These findings suggest that alginate enhances A-FMT–induced mucosal healing and that dietary fiber–microbiota interactions represent a promising adjunctive therapeutic approach for IBD. References: 1. D. Ishikawa, X. Zhang, K. Nomura, N. Seki, M. Haraikawa, K. Haga, T. Shibuya, Y. G. Kim, A. Nagahara, A randomized placebo-controlled trial of combination therapy with post-triple-antibiotic-therapy fecal microbiota transplantation and alginate for ulcerative colitis: protocol. Front Med (Lausanne) 9, 779205 (2022). 2. D. Ishikawa, H. Watanabe, K. Nomura, X. Zhang, T. Maruyama, R. Odakura, M. Koma, T. Shibuya, T. Osada, S. Fukuda, T. Nakahara, J. Terauchi, A. Nagahara, T. Yamada, Patient–donor similarity and donor-derived species contribute to the outcome of faecal microbiota transplantation for ulcerative colitis. J Crohns Colitis 19, 4: jjaf054 (2025). Conflict of interest: Dr. Odakura, Rina: No conflict of interest Ishikawa, Dai: This research was supported by AMED under Grant Number JP21ae0121038 and JSPS KAKENHI Grant Numbers JP24K11138. The joint research course with Kirin Holdings Co., Ltd. Kim, Yun-Gi: This work was supported by JSPS KAKENHI Grant Numbers JP23K27409 and JP23K18223. Nomura, Kei: No conflict of interest Zhang, Xiaochen: No conflict of interest Koma, Masao: No conflict of interest Omori, Masashi: No conflict of interest Ito, Kentaro: No conflict of interest Shibuya, Tomoyoshi: No conflict of interest Nagahara, Akihito: No conflict of interest
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