栃尾 巧

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.

Aims: To characterize fecal gut microbiota features associated with a history of aggression in dogs and to explore whether supplementation with the prebiotic fructooligosaccharide 1-kestose is associated with alterations in gut microbiota composition and owner-reported aggression-related behaviors. Study Design: An exploratory, non-randomized field study comparing aggressive and non-aggressive client-owned dogs, followed by a single-arm pre–post supplementation study in aggressive dogs with owner-reported behavioral outcomes. Place and Duration of Study: The study was conducted in Japan between 2021 and 2023, with a 60-day 1-kestose supplementation period for the intervention group. Methodology: Fecal samples from aggressive toy poodles (Agg; n = 10) and non-aggressive controls (N-Agg; n = 6) were analyzed using 16S rRNA gene sequencing. Dogs in the Agg group received 1-kestose (400 mg/day) for 60 days. Behavioral outcomes were assessed before and after supplementation using the shortened, owner-reported Canine Behavioral Assessment and Research Questionnaire (C-BARQ). Genome analysis of Blautia caecimuris was conducted to identify glycoside hydrolase family 32 (GH32) enzymes, and a recombinant GH32 enzyme was functionally characterized for fructooligosaccharide hydrolysis. Results: At baseline, Agg dogs differed in gut microbial β-diversity from N-Agg dogs and showed higher relative abundances of Mediterraneibacter gnavus, the Segatella copri group, and the Phocaeicola vulgatus group. Following 1-kestose supplementation, M. gnavus was lower, the B. caecimuris group was higher, and the β-diversity difference between groups diminished. In parallel, owner-reported aggression-related C-BARQ items—particularly responses to unfamiliar dogs and strangers near the home—were lower after supplementation. The characterized GH32 enzyme from B. caecimuris hydrolyzed 1-kestose and nystose. Conclusion: These findings indicate that 1-kestose supplementation is associated with concurrent alterations in the canine gut microbiota and owner-reported aggression-related behavioral scores. While causality cannot be established, the results support further investigation of microbiota–behavior associations using larger, well-controlled study designs incorporating objective physiological and microbial measurements.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder and typically develops later in life due to systemic dysfunction in metabolic homeostasis and various factors related to β ‐cell inflammation. Interestingly, recent studies have proposed that intra‐islet expression of inflammatory cytokines, particularly interleukin (IL)‐1 β , contributes to the pathogenesis of T2DM and have shown that blockade of IL‐1 β signaling improves glycemia and β ‐cell secretory function. We recently successfully constructed a genetically modified lactic acid bacteria (gmLAB) strain that hypersecretes recombinant mouse IL‐1 receptor antagonist (rmIL‐1Ra), that is, NZ‐IL1Ra. In this study, we investigated how NZ‐IL1Ra affects glucose metabolism using a mouse pancreatic β ‐cell line and diet‐induced obese mouse model. We found that rmIL‐1Ra purified from NZ‐IL1Ra suppresses the expression of mouse pancreatic β ‐cell genes related to inflammation. In addition, the results of oral glucose tolerance tests revealed that administration of NZ‐IL1Ra improves glucose metabolism, but the extent depends on the route of administration. Finally, microbiota analyses revealed increases in the abundances of two genera of Lachnospiraceae. These microbiota changes might also affect glucose metabolism in mice. Taken together, our results suggest that administration of NZ‐IL1Ra may be a useful tool for improving glucose metabolism.

Prebiotics, such as short- and long-chain fructans, beneficially modulate the microbiota; however, individual variability in response remains unclear. In this randomized, double-blind, placebo-controlled trial, 40 healthy adults received either a combined fructan supplement—1-Kestose (Kes) and inulin (Inu)—or a placebo (maltose + cornstarch) for 4 weeks. We investigated the fecal microbiome, bacterial growth, and glycoside hydrolase family 32 (GH32) gene abundance, and further examined the association between dietary intake and GH32. Kes and Inu co-supplementation selectively increased Bifidobacterium adolescentis and B. longum, harboring the GH32 genes inuA and cscA, respectively. Growth assays revealed that B. longum, which expresses cscA, grew only on Kes, whereas B. adolescentis, which expresses inuA, showed growth on Kes and Inu. Only responders—participants showing increases in both species—exhibited consistent upregulation of GH32 genes and were associated with higher retinol and C16:3 (n-6) fatty acid intake, as well as greater green leafy vegetable and canned tuna consumption. This study provides insights into species level responses to prebiotics, supporting personalized dietary strategies for gut microbiota modulation.

Psychiatric disorders such as major depressive disorder are closely linked to the intestinal environment, suggesting intestinal health may contribute to their prevention. Prebiotics, which enhance intestinal health, are promising candidates for preventing psychiatric disorders. 1-Kestose (kestose), a type of prebiotics, has shown potential, but its effects on psychiatric disorders remain unclear. In this study, we investigated whether kestose prevents abnormal behaviors induced by social isolation (SI) stress and which underlies mechanisms of preventive effects. C57BL/6J male mice (3 weeks old) were divided into two groups: individually housed (SI) group and housed five mice per cage (GH) group. Each group received either a normal diet or a kestose diet (5% kestose) for 5 weeks daily until the end of the behavioral testing. Kestose prevented the SI-induced abnormal behaviors including reduced sociality, impaired spatial recognition, and heightened anxiety, which were associated with suppressed microglial activation in the hippocampus. Kestose altered the diversity of gut microbiota and increased the abundance of Bacteroides sartorii. Furthermore, short-chain fatty acids (SCFAs) such as butyric acid, acetic acid, and propionic acid, produced by intestinal microbiota, were increased after kestose supplementation. Positive correlations were observed between B. sartorii abundance and SCFA levels, suggesting that B. sartorii contributes to SCFA production. Notably, both B. sartorii and SCFAs were strongly associated with the abnormal behaviors by SI. These findings suggest that kestose prevents SI-induced abnormal behaviors by modulating gut microbiota, particularly B. sartorii, through an increase of SCFA production. Taken together, kestose could be used as a promising prebiotic intervention for psychiatric disorders.