Hideaki Takahashi

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.

Aims: To evaluate the diagnostic potential of previously reported (5ar, nan) and novel microbial gene markers in fecal and salivary microbiomes for the non-invasive detection of colorectal cancer (CRC) progression. Study Design: Cross-sectional study. Place and Duration of Study: Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Japan, between June 2024 and July 2025. Methodology: Fecal samples were collected from healthy controls (n = 65) and patients with colorectal adenoma (n = 38) or carcinoma (n = 27). Salivary samples were collected from healthy controls (n = 34) and the same patient cohorts. Microbial gene abundances were quantified via quantitative PCR, and microbiome composition was assessed using 16S rRNA gene sequencing. Group comparisons used the Kruskal-Wallis and Dunn’s tests. Beta diversity differences were evaluated by PERMANOVA. Results: In fecal samples, the abundances of 5ar, nan, and the Fusicatenibacter saccharivorans 16S rRNA gene (fsr) showed a stepwise decline from the adenoma stage onward, with significantly lower levels in carcinoma versus controls (5ar, P = 0.0023; nan, P = 0.0012; fsr, P = 0.0004). Conversely, in saliva, the Fusobacterium periodonticum tyrosine phenol lyase gene (tpl) was significantly reduced only in the carcinoma group (P = 0.0180). Fecal beta diversity differed significantly between controls and both colorectal neoplasia groups (both P ≤ 0.001), whereas salivary beta diversity differed only between controls and carcinoma patients (P = 0.014). Conclusion: Fecal and salivary microbial gene markers may serve as non-invasive, rapid, and cost-effective biomarkers for colorectal neoplasia. Fecal markers captured microbiota disruption at the adenoma stage (representing the early phase of CRC progression), whereas salivary markers predominantly reflected alterations specific to carcinoma (representing the later phase). Integrating these multi-niche biomarkers provides a promising clinical platform for early detection, monitoring of precursor lesions, and postoperative surveillance; however, validation in larger, independent cohorts is warranted.

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.

Aims: Feline atopic skin syndrome (FASS) is a chronic inflammatory skin disease characterized by pruritus and typical lesions such as erythema, papules, excoriations, and lichenification. Although the relationship between gut microbiota and atopic dermatitis is well-documented in humans and dogs, research exploring gut-targeted therapies for FASS remains limited, and the role of gut microbiota in this condition is unclear. This study aimed to conduct a pilot investigation into the effects of a parasynbiotic containing 1-Kestose and heat-killed Lactobacillus plantarum FM8 on clinical symptoms and gut microbiota in cats with FASS. Methodology: Eleven cats with FASS were orally administered the parasynbiotic, composed of 1-Kestose (400 mg/day) and heat-killed Lactobacillus plantarum FM8 (2.0 × 1010 CFU/day), for 8 weeks. Clinical symptoms were assessed using the SCORing Feline Allergic Dermatitis (SCORFAD), investigator pruritus score (IPS), and rating of global assessment of improvement (GAI). Fecal microbiota was analyzed at baseline and post-intervention using 16S rRNA sequencing, with samples from 16 healthy cats as controls. Results: Parasynbiotic intervention significantly reduced SCORFAD and IPS scores (p = 0.0224 and p = 0.0018, respectively), and improvement in GAI scores was observed in 10 of 11 cats. Additionally, β-diversity analysis of fecal microbiota did not reveal significant differences between baseline and post-intervention samples within the FASS group, a trend toward distinction from healthy controls was observed. Taxonomic analysis revealed that Collinsella stercoris was significantly enriched in FASS cats compared with healthy controls, whereas its abundance decreased significantly after parasynbiotic intervention. Conclusion: These findings suggested that improvements in clinical symptoms may be linked to alterations in gut microbiota, specifically through the reduction of C. stercoris, which was initially enriched in FASS cats. This pilot study underscores the potential of parasynbiotic administration as a therapeutic strategy for FASS, while its small sample and lack of placebo control warrant cautious interpretation.