高橋 秀明

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.

Background/Objectives: Nopalea cochenillifera (L.) Salm-Dyck cladodes are rich in dietary fiber, polyphenols, and minerals, which are known to exert antioxidant and immunomodulatory effects. However, the mechanisms and active constituents have not been fully elucidated. In this study, we investigated the effects of continuous N. cochenillifera consumption on lipid metabolism, immune function, and the gut microbiota in mice. Methods: The feed was made using freeze-dried and powdered cladodes of N. cochenillifera. Male C57BL/6J mice were assigned to four groups: control diet (C), control diet plus 10% N. cochenillifera (CN), high-fat diet (FC), and high-fat diet plus 10% N. cochenillifera (FN). Results: Cactus supplementation reduced the body and liver weights that were elevated by the high-fat diet. Serum total cholesterol and free fatty acids were increased in the FC group compared with the C group, while cactus intake lowered these levels and enhanced fecal cholesterol excretion. Cactus consumption also elevated fecal total IgA and mucin contents. IL-4 expression in Peyer’s patches was significantly increased in the FN group compared with the FC group. Gut microbiota analysis showed significant differences in β-diversity, along with increased α-diversity and higher abundance of Lachnospiraceae, following cactus intake. Conclusions: These findings suggest that N. cochenillifera intake increases gut microbiota diversity, which enhances intestinal barrier function and thereby contributes to improved lipid metabolism and immune regulation.

Introduction. Gastrectomy considerably affects the gut microbiome; however, the association between dysbiosis and post-gastrectomy syndrome remains to be explored. This study prospectively explored fecal gut microbiota alterations before and 3 months after gastrectomy, investigating their potential association with weight loss.Methods. The gut microbiome of 21 patients with gastric cancer scheduled for gastrectomy in April–October 2022 was analyzed using 16S rRNA gene Next-Generation Sequencing. Their microbiome profiles were compared to those of healthy controls. Bacterial taxa demonstrating significant changes were determined using the Linear Discriminant Analysis Effect Size algorithm and further analyzed for their relationship with weight loss in the gastrectomy cohort.Results. Postoperative complications (≥grade 2) were observed in 14.3% of patients. Postoperative weight loss was －10.9%, with the following breakdown: distal (－7.0%), total (－13.5%), and proximal (－14.0%) gastrectomy (P = 0.003). Microbiota analysis demonstrated a significant incline in the abundance of the Streptococcus salivarius group and a decline in Bacteroides uniformis in patients with gastric cancer compared to healthy controls. The S. salivarius group exhibited a further increase, while B. uniformis showed signs of recovery after gastrectomy. Additionally, 5α-reductase gene levels, reported to decrease as several cancers progress, were found to elevate post-surgery. Furthermore, patients experiencing greater weight loss showed a significant reduction in Faecalibacterium prausnitzii levels, while lower serum prealbumin and zinc levels were associated with the abundance of Escherichia coli.Conclusion. Gastrectomy significantly alters the gut microbiome. Supporting microbiome health with prebiotics may help alleviate postoperative issues and improve patients' quality of life.

Recent studies have linked Ruminococcus gnavus to inflammatory bowel disease and Fusobacterium nucleatum to various cancers. Agarooligosaccharides (AOS), derived from the acid hydrolysis of agar, have shown significant inhibitory effects on the growth of R. gnavus and F. nucleatum at concentrations of 0.1 and 0.2%, respectively. RNA sequencing and quantitative reverse-transcription PCR analyses revealed the downregulation of fatty acid biosynthesis genes (fab genes) in these bacteria when exposed to 0.1% AOS. Furthermore, AOS treatment altered the fatty acid composition of R. gnavus cell membranes, increasing medium-chain saturated fatty acids (C8, C10) and C18 fatty acids while reducing long-chain fatty acids (C14, C16). In contrast, no significant growth inhibition was observed in several strains of Bifidobacteria and Lactobacillales at AOS concentrations of 0.2 and 2%, respectively. Co-culture experiments with R. gnavus and Bifidobacterium longum in 0.2% AOS resulted in B. longum dominating the population, constituting over 96% post-incubation. In vivo studies using mice demonstrated a significant reduction in the Lachnospiraceae family, to which R. gnavus belongs, following AOS administration. Quantitative PCR also showed lower levels of the nan gene, potentially associated with immune disorders, in the AOS group. These findings suggest that AOS may introduce a novel concept in prebiotics by selectively inhibiting potentially pathogenic bacteria while preserving beneficial bacteria such as Bifidobacteria and Lactobacillales.

Less than half of all patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) respond to chemotherapy, and the prognosis of PDAC is poor, which may be mediated by the gut microbiota. We investigated the clinical improvement effects of 1-kestose, a fructooligosaccharide, on PDAC chemotherapy in this single-center, randomized, controlled pilot trial conducted at Fujita Health University Hospital, which enrolled patients with PDAC. The trial included 1-kestose administration and non-administration groups. The 1-kestose group received 9 g of 1-kestose daily for 12 weeks, and their blood markers, imaging studies, physical findings, and gut microbiota were evaluated. In the 1-kestose administration group, the cancer marker CA19-9 significantly decreased, and there was a reduction in the neutrophil-to-lymphocyte ratio (NLR). There was also suppression of the reduction of albumin levels and of an increase in C-reactive protein. Additionally, Escherichia coli, which typically increases in PDAC, significantly decreased in the 1-kestose group. Thus, 1-kestose altered the gut microbiota and improved the prognostic factors for PDAC. Large-scale, long-term trials of 1-kestose interventions for PDAC are thus warranted to improve the prognosis of PDAC.

Abstract Background It has become clear that the intestinal microbiota plays a role in food allergies. The objective of this study was to assess the food allergy-preventive effects of combined intake of a short fructan (1-kestose [Kes]) and a long fructan (inulin ([Inu]) in an ovalbumin (OVA)-induced food allergy mouse model. Results Oral administration of fructans lowered the allergenic symptom score and alleviated the decreases in rectal temperature and total IgA levels and increases in OVA-specific IgE and IgA levels induced by high-dose OVA challenge, and in particular, combined intake of Kes and Inu significantly suppressed the changes in all these parameters. The expression of the pro-inflammatory cytokine IL-4, which was increased in the allergy model group, was significantly suppressed by fructan administration, and the expression of the anti-inflammatory cytokine IL-10 was significantly increased upon Kes administration. 16 S rRNA amplicon sequencing of the gut microbiota and beta diversity analysis revealed that fructan administration may induce gut microbiota resistance to food allergy sensitization, rather than returning the gut microbiota to a non-sensitized state. The relative abundances of the genera Parabacteroides B 862,066 and Alloprevotella, which were significantly reduced by food allergy sensitization, were restored by fructan administration. In Parabacteroides, the relative abundances of Parabacteroides distasonis, Parabacteroides goldsteinii, and their fructan-degrading glycoside hydrolase family 32 gene copy numbers were increased upon Kes or Inu administration. The concentrations of short-chain fatty acids (acetate and propionate) and lactate were increased by fructan administration, especially significantly in the Kes + Inu, Kes, and Inu-fed (Inu, Kes + Inu) groups. Conclusion Combined intake of Kes and Inu suppressed allergy scores more effectively than single intake, suggesting that Kes and Inu have different allergy-preventive mechanisms. This indicates that the combined intake of these short and long fructans may have an allergy-preventive benefit.