Clinical and Microbial Insights into the Therapeutic Potential of 1-Kestose in Managing Crohn’s Disease

Background and Aims: Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by gastrointestinal inflammation, with gut microbiota dysbiosis playing a key role in its onset and progression. This study aimed to evaluate whether 1-kestose supplementation modulates gut microbiota composition and mucin degradation–related biomarkers in patients with clinically inactive to mild CD, and to explore plausible ecological mechanisms in vitro. Study Design: Single-arm pilot intervention study with exploratory laboratory experiments. Place and Duration of Study: Samples were collected at Tokai University Hospital (Japan), and microbiome/qPCR analyses and in vitro assays were performed at Fujita Health University (Japan). The supplementation period was four months. Methodology: Nineteen patients with clinically inactive to mild CD (CDAI ≤ 220) received 1-kestose (3 g) twice daily for 4 months. Fecal microbiota composition was assessed by 16S rRNA gene sequencing, and qPCR quantified nanA homologs (nan levels) as a functional marker related to mucin-degrading potential. Clinical biomarkers (CDAI, fecal calprotectin, CRP, albumin) were monitored. To investigate potential mechanisms, in vitro cultures of Ruminococcus gnavus and Bifidobacterium longum were performed under sugar-supplemented conditions, including 1-kestose, and growth responses were evaluated; short-chain fatty acids (SCFAs) were descriptively assessed in pooled culture supernatants. Results: Clinical biomarkers remained stable throughout supplementation. 1-kestose intake was associated with an increased relative abundance of Bifidobacterium and a decreased abundance of Blautia, along with reduced fecal nan levels. In vitro, B. longum showed enhanced early growth with 1-kestose compared with other sugars, whereas R. gnavus exhibited impaired growth under acidic conditions. Exploratory SCFA measurements suggested higher acetate in sugar-supplemented B. longum cultures. Conclusion: In this single-arm pilot cohort of patients with clinically inactive to mild CD, 1-kestose supplementation was associated with shifts toward potentially beneficial taxa and a reduction in nan levels, a functional marker linked to mucin-degrading potential. These findings, supported by exploratory in vitro observations, suggest that 1-kestose may modulate gut ecological conditions; however, clinical efficacy and causality require confirmation in randomized, placebo-controlled trials with detailed dietary and medication monitoring.