藤井 匡

BackgroundParkinson's disease (PD) is a multifactorial neurodegenerative disorder increasingly linked to gut microbiota alterations. However, despite advances in fecal microbiota profiling as a non-invasive approach to disease risk assessment, its clinical utility remains limited by a lack of functionally relevant microbial biomarkers.ObjectiveThis cross-sectional study aimed to identify a microbial gene marker reflecting metabolic potential associated with both the presence and severity of PD.MethodsFecal samples from patients with PD (n = 59) and healthy controls (n = 65) were analyzed by 16S rRNA sequencing to characterize taxonomic profiles. Quantitative PCR (qPCR) targeted the consensus sequence of the mucin-degrading nanA gene (nanAkk), a highly conserved within Akkermansia nan gene clusters. Differences in taxonomic composition and nanAkk abundance were examined, and correlations with clinical severity scores evaluated in the PD group.ResultsPatients with PD showed reduced abundance of short-chain fatty acid-producing taxa (Faecalibacterium, Blautia, and Anaerostipes) and increased levels of Akkermansia. Akkermansia abundance correlated positively with motor severity, including Hoehn-Yahr stage. Moreover, nanAkk levels also correlated positively with Hoehn-Yahr stage and were significantly elevated in PD patients compared with controls. Levels in the stage 4-5 group exceeded those in the stage 1-3 group (P = 0.0202), indicating a stage-related increase in mucin-degrading nanAkk abundance.ConclusionsWe have identified nanAkk as a microbial gene marker associated with both the presence and severity of PD. Our qPCR-based quantification shows potential as a non-invasive biomarker for disease stratification.

Gut microbiota dysbiosis is implicated in diverse intestinal and systemic disorders, and prebiotics offer a practical strategy to modify host–microbe interactions. This review evaluates 1-kestose as a candidate precision bioactive component by integrating its chemical structure, enzymatic production, gastrointestinal fate, GH32-dependent microbial utilization, human evidence, and qPCR-based response monitoring. Many commercial fructooligosaccharides contain molecules with different degrees of polymerization, complicating structure–function interpretation. In contrast, 1-kestose is a high-purity trisaccharide fructooligosaccharide and the shortest member of the inulin-type fructans. By comparing 1-kestose with long-chain inulin, we examine how fructan chain length may influence colonic fermentation kinetics, substrate availability, and tolerability. We then discuss the role of GH32 substrate specificity in the selective microbial utilization of 1-kestose and related fructooligosaccharides, particularly by bifidobacteria and representative butyrate producers. Next, we review the mechanistic rationale and preclinical evidence for co-administration of 1-kestose and long-chain inulin. Human intervention studies have evaluated 1-kestose across gastrointestinal, metabolic, immune-related, neonatal, oncological, and bowel-habit contexts, with emerging evidence of potential benefits. One healthy-adult trial has also evaluated co-administration with long-chain inulin, although direct comparative trials remain an important future priority. Finally, we propose a research framework that integrates high-purity 1-kestose, GH32-dependent microbial selectivity, and qPCR-based baseline stratification and response monitoring. Prospective, independently replicated trials are needed to establish clinical effectiveness and determine the value of biomarker-guided intervention and combination strategies.

Abstract The gut microbiome is a potential source of non-invasive cancer biomarkers. We evaluated six fecal microbial markers and developed targeted qPCR-based logistic models for colorectal cancer (CRC) and pancreatic cancer (PC). Using LASSO with the 1-standard-error rule, four markers were selected for CRC (afb, nan, fsr, and 5ar) and three for PC (but, fsr, and saa). In post-selection leave-one-out cross-validation of fixed model structures, the CRC and PC models yielded AUCs of 0.824 and 0.780, respectively. Fixed-model application yielded AUCs of 0.716 for colorectal adenoma and 0.540 for the pancreatic high-risk group. In an exploratory Early PC versus high-risk comparison, the fecal qPCR score showed a higher AUC point estimate than CA19-9, while the difference was not statistically significant. Overall, the disease-specific model performance and fixed-model behavior across clinically related groups support further evaluation of model-derived cancer probability scores as exploratory cancer-assessment tools.

Background: Agaro-oligosaccharides (AOS) have been shown to modulate the gut microbiota in in vitro and animal studies; however, human evidence remains scarce. Methods: Herein, we conducted a four-week open-label, single-arm, non-randomized pilot trial in 18 healthy Japanese adults to examine the association of AOS intake at 200 mg/day with gut microbiota composition and bowel condition. Fecal samples collected before and after the intervention were analyzed using QIIME2-based 16S rRNA sequencing, and bowel condition was assessed with the Bristol Stool Form Scale. This study was registered in the UMIN Clinical Trials Registry (UMIN000056992). Results: AOS intake was not associated with significant changes in bowel condition. Gut microbiota analysis showed no significant alterations in overall community structure but revealed taxon-specific trends in the relative abundance of several bacterial taxa. Notably, nominal changes were observed in the abundance of the Ruminococcus gnavus group and Bacteroides uniformis after the intervention. In addition, quantitative PCR analysis showed an increase in 3,6-anhydro-L-galactose cycloisomerase (ACI) gene abundance after the intervention. Conclusions: These findings suggest that, in this exploratory pilot study, AOS intake was associated with a taxon-specific pattern in the gut microbiota. Further randomized controlled studies are needed to clarify the microbiota-related effects of AOS in humans.

Background & Aims: Age-related variation in the gut microbiota complicates biomarker discovery for pancreatic cancer. This study aimed to identify microbial taxa with minimal age dependence that are associated with pancreatic neoplasia and to develop a practical quantitative PCR (qPCR)-based assay targeting a shared gene involved in butyrate production. Study design: Cross-sectional study. Place and Duration of Study: Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Japan, between October 2022 and July 2025. Methodology: Fecal samples from 64 individuals with precursor lesions considered to be at high risk for pancreatic cancer (HR) and 22 patients with pancreatic cancer (PC) were compared with those from healthy controls aged <50 years (Young; n = 71) and ≥50 years (Old; n = 65). Microbiota composition was analyzed by 16S rRNA gene sequencing. A qPCR primer set targeting the but gene, which encodes butyryl-CoA:acetate CoA-transferase, was designed to evaluate the shared genetic potential of the identified minimally age-dependent taxa, namely the Anaerostipes hadrus group and Agathobacter rectalis. Results: The A. hadrus group and A. rectalis showed disease-associated depletion with minimal age dependency. The qPCR assay showed no difference in but gene levels between the Young and Old groups (P = 0.3301). but gene levels in the HR group were comparable to those in the Old group (P > 0.9999), whereas levels in the PC group were significantly lower than those in the Old group (P = 0.0020) and the HR group (P = 0.0136). Conclusion: Targeting the but gene provides a practical approach to assessing the shared butyrate-producing potential of this minimally age-dependent microbial cluster. Within this cross-sectional cohort, but gene levels were preserved in HR individuals, whereas levels in the PC group were reduced, suggesting its potential utility as a non-invasive adjunct for future evaluation in longitudinal monitoring or risk assessment after prospective validation.