Clinical and Microbial Insights into the Therapeutic Potential of 1-Kestose in Managing Crohn’s Disease
Tadashi Fujii *
Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan, Department of Medical Research on Prebiotics and Probiotics, Fujita Health University, Toyoake, Aichi, Japan and BIOSIS Lab. Co., Ltd., Toyoake, Aichi, Japan.
Takumi Tochio
Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan, Department of Medical Research on Prebiotics and Probiotics, Fujita Health University, Toyoake, Aichi, Japan and BIOSIS Lab. Co., Ltd., Toyoake, Aichi, Japan.
Erika Teramura
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
Masaya Sano
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
Mia Fujisawa
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
Takayoshi Suzuki
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University Hachioji Hospital, Hachioji, Japan.
Kohei Funasaka
Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Eizaburo Ohno
Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Yoshiki Hirooka
Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan, Department of Medical Research on Prebiotics and Probiotics, Fujita Health University, Toyoake, Aichi, Japan and BIOSIS Lab. Co., Ltd., Toyoake, Aichi, Japan.
Masashi Matsushima
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
*Author to whom correspondence should be addressed.
Abstract
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.
Keywords: Bifidobacterium longum, Crohn’s disease, 1-kestose, nan levels, Ruminococcus gnavus