講演情報
[SY7-3]Microbiome Determinants of Sustained Remission after Antibiotic-Preconditioned FMT in Ulcerative Colitis: A Prospective Multicenter Study with One-Year Follow-up
*Sayaka Mizutani1, Kei Nomura1,2, Masayuki Orikasa2, Masashi Omori2, Rina Odakura2, Masao Koma2, Takafumi Maruyama2, Kentaro Ito2, Tomoyoshi Shibuya2, Gaku Nakato1, Hikaru Watanabe3, Douaa Zakaria3, Akihito Nagahara1,2, Dai Ishikawa1,2,3 (1. Innovative Microbiome Therapy Research Center, Juntendo University Graduate School of Medicine, Japan, 2. Department of Gastroenterology, Juntendo University Faculty of Medicine, 3. Metagen Therapeutics, Inc.)
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing and remitting inflammation of the colonic mucosa. Although its pathogenesis remains incompletely understood, UC is thought to arise from complex interactions among genetic susceptibility, immune dysregulation, and environmental factors. Accumulating evidence indicates that intestinal dysbiosis is a hallmark of UC, with patients showing reduced microbial diversity and disruption of the normal microbial community structure compared with healthy individuals.
To address this, we developed antibiotic-preconditioned fecal microbiota transplantation (A-FMT), combining a 2-week course of amoxicillin, fosfomycin, and metronidazole (AFM) with anaerobically prepared FMT. A-FMT was administered as repeated FMT consisting of one colonoscopic infusion followed by two enemas. This strategy was designed to reduce colonization resistance, preserve oxygen-sensitive donor microbes, and enhance donor microbial engraftment.
To evaluate efficacy and safety, we performed a prospective multicenter study of A-FMT. Clinical remission at week 8, short-term safety, donor microbial convergence, and exploratory microbiome signatures associated with remission were assessed. Seventeen of 37 treated patients (45.9%) achieved clinical remission at week 8, exceeding the rate reported in a historical placebo cohort from a Japanese budesonide foam trial (20.5%).
Despite remission at week 8, maintenance of long-term remission remains an unmet medical need, as some patients experience subsequent clinical deterioration. Therefore, as a follow-up to the above study, we conducted an additional longitudinal investigation focusing on microbiome determinants of sustained versus non-sustained remission.
Here we present longitudinal findings from this extension study, in which stool samples were collected and shotgun metagenomic analyses were performed for up to one year after FMT to characterize microbiome differences between patients with sustained and non-sustained long-term remission.
To address this, we developed antibiotic-preconditioned fecal microbiota transplantation (A-FMT), combining a 2-week course of amoxicillin, fosfomycin, and metronidazole (AFM) with anaerobically prepared FMT. A-FMT was administered as repeated FMT consisting of one colonoscopic infusion followed by two enemas. This strategy was designed to reduce colonization resistance, preserve oxygen-sensitive donor microbes, and enhance donor microbial engraftment.
To evaluate efficacy and safety, we performed a prospective multicenter study of A-FMT. Clinical remission at week 8, short-term safety, donor microbial convergence, and exploratory microbiome signatures associated with remission were assessed. Seventeen of 37 treated patients (45.9%) achieved clinical remission at week 8, exceeding the rate reported in a historical placebo cohort from a Japanese budesonide foam trial (20.5%).
Despite remission at week 8, maintenance of long-term remission remains an unmet medical need, as some patients experience subsequent clinical deterioration. Therefore, as a follow-up to the above study, we conducted an additional longitudinal investigation focusing on microbiome determinants of sustained versus non-sustained remission.
Here we present longitudinal findings from this extension study, in which stool samples were collected and shotgun metagenomic analyses were performed for up to one year after FMT to characterize microbiome differences between patients with sustained and non-sustained long-term remission.