藤井 匡

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.

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: Ventilator-associated pneumonia (VAP) after tracheal intubation is a major infectious complication in patients in the intensive care unit (ICU), with an incidence of 8-28%. Oral care in the ICU is essential; however, the presence of an intubation tube and restricted mouth opening cause complications. A healthy commensal microflora in the oral cavity resists colonization by respiratory pathogens, and poor oral hygiene may increase the risk for VAP. In this study, we examined the effectiveness of oral care on oral bacterial counts and microbial diversity in patients admitted to the ICU. METHODS: Fifteen ICU patients were included in this study. Oral microbiome samples were collected by swabbing the surface of the tongue. Oral bacterial counts were measured at four time points: before and after oral care, both pre- and post-extubation. Additionally, microbiome analysis was conducted twice: once before oral care pre-extubation, and once before oral care post-extubation. Oral bacterial counts were assessed using a bacterial counter, and microbiome analysis was performed through 16S rRNA gene amplicon sequencing. RESULTS: Oral bacterial counts significantly decreased after oral care at both pre- and post-extubation time points. Microbiome analysis revealed significant differences in alpha diversity pre- and post-extubation samples. Samples post extubation were less diverse. CONCLUSIONS: This study demonstrates that oral care effectively reduces bacterial counts in ICU patients, both pre- and post-extubation. Microbiome analysis revealed shifts in microbial diversity, suggesting that the oral microbiota was disrupted during intubation. Given the risk of VAP, oral care may play an important role to prevent VAP in ICU settings.

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.